National Cancer Institute®
Last Modified: January 1, 2002
UI - 11588060
AU - Samorapoompichit P; Kiener HP; Schernthaner GH; Jordan JH; Agis H;
TI - Wimazal F; Baghestanian M; Rezaie-Majd A; Sperr WR; Lechner K; Valent P Detection of tryptase in cytoplasmic granules of basophils in patients with chronic myeloid leukemia and other myeloid neoplasms.
SO - Blood 2001 Oct 15;98(8):2580-3
AD - Institute of Histology and Embryology, Department of Internal Medicine I, University of Vienna, Vienna, Austria.
Tryptases are serine proteases primarily expressed in mast cells. Normal blood basophils express only trace amounts of the enzyme. However, recent immunohistochemical studies have raised the possibility that neoplastic basophils express significant amounts of tryptase. In this study, tryptase expression was analyzed in normal and neoplastic basophils by immunoelectron microscopy using antitryptase monoclonal antibody G3. Basophils were obtained from patients with chronic myeloid leukemia (CML), idiopathic myelofibrosis (IMF), and myelodysplastic syndrome (MDS), and from healthy donors. Tryptase-immunoreactive material was detected in cytoplasmic granules of basophils in CML, IMF, and MDS. By contrast, normal basophils did not contain significant amounts of tryptase by immunoelectron microscopy. As assessed by reverse transcription-polymerase chain reaction, neoplastic basophils contained messenger RNA (mRNA) for alpha-tryptase, but no beta-tryptase mRNA. In summary, these data provide evidence that neoplastic basophils in CML, IMF, and MDS can express detectable amounts of tryptase. Therefore, tryptase should not be regarded as specific for mast cells when neoplastic myeloid cells are analyzed.
UI - 11605570
AU - Vargas H; Jennings TA; Galati LT
TI - Unusual paranasal sinus tumors in two patients with common nasal complaints.
SO - Ear Nose Throat J 2001 Oct;80(10):724-6, 728-9
AD - Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Albany Medical College, 47 New Scotland Ave., MC41, Albany, NY 12208, USA.
Common nasal complaints are managed by both the otolaryngologist and the primary care physician. We describe the cases of two patients with nasal obstruction who were referred to us for evaluation--one with severe headache and the other with profuse epistaxis. Their histories prior to referral included long-term, common rhinologic complaints of low-grade headache and mild epistaxis. Neither patient had been referred to us until their symptoms had become severe. Our examination revealed that both patients had rare paranasal sinus pathology. One patient had a fibroxanthoma of the frontal sinus, and the other had extramedullary hematopoiesis of the maxillary sinus. Fibroxanthoma of the frontal sinus is rare, and extramedullary hematopoiesis of the maxillary sinus has not been previously reported. These two unique cases serve as a reminder that long-term common rhinologic complaints can occasionally be a sign of life-threatening pathology and require a full evaluation by an otolaryngologist.
UI - 11640868
AU - Bench AJ; Cross NC; Huntly BJ; Nacheva EP; Green AR
TI - Myeloproliferative disorders.
SO - Best Pract Res Clin Haematol 2001 Sep;14(3):531-51
AD - Department of Haematology, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2XY, UK.
The myeloproliferative disorders (MPDs) are a group of pre-leukaemic disorders characterized by proliferation of one or more lineages of the myelo-erythroid series. Unlike the Philadelphia chromosome in chronic myeloid leukaemia, there is no pathognomonic chromosomal abnormality associated with the MPDs. Chromosomal abnormalities are seen in 30-40% of patients with polycythaemia vera (PV) and idiopathic myelofibrosis (IMF) and seem to indicate a poor prognosis. On the other hand, chromosomal abnormalities are rare in essential thrombocythaemia. Consistent acquired changes seen at diagnosis include deletion of the long arm of chromosome 20, del(13q), trisomy 8 and 9 and duplication of parts of 1q. Furthermore del(20q), trisomy 8 and dupl(lq) all arise in multipotent progenitor cells. Molecular mapping of 20q deletions and, to some extent, 13q deletions has identified a number of candidate target genes, although no mutations have yet been found. Finally, translocations associated with the rare 8p11 myeloproliferative syndrome and other atypical myeloproliferative disorders have permitted the identification of a number of novel fusion proteins involving fibroblast growth factor receptor-1. Copyright 2001 Harcourt Publishers Ltd.
UI - 11551897
AU - Hodge DR; Xiao W; Clausen PA; Heidecker G; Szyf M; Farrar WL
TI - Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells.
SO - J Biol Chem 2001 Oct 26;276(43):39508-11
AD - Intramural Research Support Program, SAIC Frederick, NCI-Frederick Cancer Research and Development Center, National Institutes of Health, Frederick, MD 21702, USA. firstname.lastname@example.org
Methylation of mammalian DNA by the DNA methyltransferase enzyme (dnmt-1) at CpG dinucleotide sequences has been recognized as an important epigenetic control mechanism in regulating the expression of cellular genes (Yen, R. W., Vertino, P. M., Nelkin, B. D., Yu, J. J., el-Deiry, W., Cumaraswamy, A., Lennon, G. G., Trask, B. J., Celano, P., and Baylin, S. B. (1992) Nucleic Acids Res. 20, 2287-2291; Ramchandani, S., Bigey, P., and Szyf, M. (1998) Biol. Chem. 379, 535-5401). Here we show that interleukin (IL)-6 regulates the methyltransferase promoter and resulting enzyme activity, which requires transcriptional activation by the Fli-1 transcription factor (Spyropoulos, D. D., Pharr, P. N., Lavenburg, K. R., Jackers, P., Papas, T. S., Ogawa, M., and Watson, D. K. (1998) Mol. Cell. Biol. 15, 5643-5652). The data suggest that inflammatory cytokines such as IL-6 may exert many epigenetic changes in cells via the regulation of the methyltransferase gene. Furthermore, IL-6 regulation of transcription factors like Fli-1, which can help to direct cells along opposing differentiation pathways, may in fact be reflected in part by their ability to regulate the methylation of cellular genes.
UI - 11675138
AU - Paulsson K; Sall T; Fioretos T; Mitelman F; Johansson B
TI - The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology.
SO - Cancer Genet Cytogenet 2001 Oct 15;130(2):160-5
AD - Department of Clinical Genetics, Lund University Hospital, SE-221 85, Lund, Sweden. email@example.com
Although trisomy 8 as a sole change is one of the most common chromosomal abnormalities in myeloid malignancies, it is largely unknown if the incidence of this aberration is influenced by other factors of clinical importance. In the present study, the frequencies of isolated +8 in relation to gender, age, previous treatment with chemo- or radiotherapy, and morphologic subtype were ascertained in published, as well as in our own unpublished, cases of acute myeloid leukemia (AML; n=4,246), myelodysplastic syndromes (MDS; n=1,817), and chronic myeloproliferative disorders (MPD; n=530). The frequencies of +8 were higher in MDS and MPD than in AML (7.5% vs. 5.6%; P<0.01) and varied among the morphologic subtypes of AML and MDS (P<0.001 and P<0.05, respectively). Trisomy 8 was more common in women than in men with MPD (11% vs. 5.1%; P<0.05). Furthermore, the frequencies of +8 were higher in de novo AML and MDS than in treatment-related cases (6.0% vs. 2.8%; P<0.01 and 8.6% vs. 1.5%; P<0.001, respectively). The incidence also varied significantly with age in AML (P<0.001), being more common in elderly patients. Although the causes for this frequency heterogeneity remain to be elucidated, possible explanations may include different environmental exposures affecting the origin of +8 in AML, MDS, and MPD and the presence of different underlying cryptic primary aberrations.
UI - 11703326
AU - Canepa L; Ballerini F; Varaldo R; Quintino S; Reni L; Clavio M; Miglino
TI - M; Pierri I; Gobbi M Thalidomide in agnogenic and secondary myelofibrosis.
SO - Br J Haematol 2001 Nov;115(2):313-5
AD - Department of Internal Medicine, University of Genova, Genova, Italy.
Myelofibrosis with myeloid metaplasia (MMM) is a clonal disorder involving disregulation of angiogenesis and immunomodulatory mechanisms. Thalidomide (Thal) retains antiangiogenic, immunomodulatory and cytokine regulatory properties and recently it has been used successfully in multiple myeloma. Here, we report our experience in 10 MMM patients treated with Thal. Patients with agnogenic MMM treated in an early phase of the disease obtained significant benefits from the therapy and remain transfusion-free. In contrast, all secondary MMM failed to respond. These preliminary findings confirm that Thal plays a role in MMM therapy, although the efficacy in the different phases of the disease must be further evaluated.
UI - 11703327
AU - Tefferi A; Meyer RG; Wyatt WA; Dewald GW
TI - Comparison of peripheral blood interphase cytogenetics with bone marrow karyotype analysis in myelofibrosis with myeloid metaplasia.
SO - Br J Haematol 2001 Nov;115(2):316-9
AD - Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
In a prospective study of 42 patients with myelofibrosis with myeloid metaplasia (MMM), peripheral blood (PB) and bone marrow (BM) interphase cytogenetics and PB CD34 enumeration were performed concomitantly with BM karyotype analysis. Interphase cytogenetics was performed with a panel of fluorescence in situ hybridization (FISH) probes that were capable of detecting most of the known recurrent cytogenetic lesions in MMM. There was a close concordance in the results of interphase cytogenetics between PB and BM, regardless of the PB CD34 count. In general, FISH-detectable abnormalities were also detected by BM karyotype. Although complementary, interphase cytogenetics may not always provide the necessary karyotypic information in MMM.
UI - 11703351
AU - Hattori H; Matsuzaki A; Suminoe A; Ihara K; Nakayama H; Hara T
TI - High expression of platelet-derived growth factor and transforming growth factor-beta 1 in blast cells from patients with Down Syndrome suffering from transient myeloproliferative disorder and organ fibrosis.
SO - Br J Haematol 2001 Nov;115(2):472-5
AD - Department of Paediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. firstname.lastname@example.org
To determine whether platelet-derived growth factor (PDGF) and transforming growth factor-beta 1 (TGF-beta 1) are involved in organ fibrosis in patients with transient myeloproliferative disorder (TMD) in Down syndrome, the expression of PDGF and TGF-beta 1 mRNA in blast cells of TMD was investigated using real-time quantitative reverse transcription polymerase chain reaction. Blasts and liver tissue from TMD patients with hepatic fibrosis showed a significantly elevated expression of PDGF gene. The expression of TGF-beta 1 gene was higher in TMD and acute megakaryoblastic leukaemia than in the control group. These results suggest that PDGF in combination with TGF-beta 1 plays a role in organ fibrosis of TMD.
UI - 11737254
AU - Hirose Y; Masaki Y; Shimoyama K; Sugai S; Nojima T
TI - Granulocytic sarcoma of megakaryoblastic differentiation in the lymph nodes terminating as acute megakaryoblastic leukemia in a case of chronic idiopathic myelofibrosis persisting for 16 years.
SO - Eur J Haematol 2001 Sep;67(3):194-8
AD - Division of Hematology and Immunology, Department of Internal Medicine, Kanazawa Medical University, Ishikawa, Japan.
A 43-yr-old Japanese woman presented with mild anemia, leukocytosis and lymphadenopathy. Biopsy of the lymph node revealed infiltration of blasts, megakaryocytes, fibroblasts and myeloid cells. Large blasts with basophilic cytoplasm with cytoplasmic projections appeared in the peripheral blood. These blasts were negative in peroxidase stain, positive in acid phosphatase and weakly positive in periodic acid-Schiff stain. Immunohistochemical staining with monoclonal antibodies revealed that these blasts were positive with anti-CD41 (glycoprotein IIb/IIIa) and negative with other monoclonal antibodies. So diagnosis of granulocytic sarcoma in megakaryoblastic transformation from chronic idiopathic myelofibrosis was made. A cytogenetic study revealed that bone marrow cells were 46,XX del(13)(q?) initially and additional abnormalities including der(5,5,11)(q11;q13)ins(5;?)(q11;?) were found when she developed megakaryoblastic transformation. Granulocytic sarcoma of megakaryoblastic transformation from chronic idiopathic myelofibrosis is a rare event. Immunophenotyping with monoclonal antibody for CD41(glycoprotein IIb/IIIa) confirmed the diagnosis.
UI - 11378575
AU - Andreasson B; Lindstedt G; Stockelberg D; Wadenvik H; Kutti J
TI - The relation between plasma thrombopoietin and erythropoietin concentrations in polycythaemia vera and essential thrombocythaemia.
SO - Leuk Lymphoma 2001 May;41(5-6):579-84
AD - Department of Medicine, Sahlgrenska University Hospital, University of Goteborg, Sweden.
Plasma thrombopoietin (TPO) was measured, by immunoenzymometric assay, in 39 patients with polycythaemia vera (PV), 33 patients with essential thrombocythaemia (ET) and 10 healthy volunteers. The mean TPO concentration was significantly higher in ET patients than in PV patients (p=0.04) and normals (p<0.001). The 6 untreated ET patients had a significantly lower mean TPO concentration compared to the 27 ET patients who were on myelosuppressive regimens (p=0.01). The mean plasma TPO for the 5 PV patients treated with phlebotomy only did not differ significantly from the corresponding mean for the 34 PV patients treated with myelosuppressive agents. Concomitantly, plasma EPO was measured in 25 of the PV patients and in 30 of the ET patients by an immunoradiometric assay with normal reference interval in adults 3.7-16 IU/L. In the 14 PV patients with EPO <3.7 IU/L mean plasma TPO did not differ significantly from the mean for the 11 PV patients with EPO >or=3.7 IU/L; neither of these two groups had plasma TPO concentrations significantly different from the mean for the control subjects. The 7 ET patients with subnormal plasma EPO had significantly lower mean plasma TPO compared to the ET patients with normal and high plasma EPO concentrations (p=0.03 and p=0.02, respectively). Also, the 16 ET patients with normal plasma EPO had significantly lower plasma TPO compared to the 8 patients with high plasma EPO (p=0.04). The mean plasma TPO for each of these three groups of ET patients was significantly higher than the corresponding mean for the controls (p<0.001 for each group). The results of the present study indicate that a relationship between plasma EPO and TPO concentrations may exist and that myelosuppressive treatment affects the TPO concentration in ET but not in PV patients.
UI - 11713378
AU - Quaglino D; Di Leonardo G; Stati M
TI - Leukaemic transformation in a case of thrombocythaemia. Case report and review of the literature.
SO - Acta Haematol 2001;106(3):122-5
AD - Clinica Medica II, Universita degli Studi de L'Aquila, Italia.
The authors describe a case of thrombocythaemia, with subsequent leukaemic transformation. Cytochemical and immunocytochemical investigations indicated a trilineage involvement of the myeloid series, compatible with a leukaemic transformation at the level of the colony-forming unit granulocytes, erythrocytes, macrophages, megakaryocytes. No cytogenetic abnormalities were observed. The criteria which have been proposed to differentiate essential thrombocythaemia from pre-fibrotic thrombocythaemia, as an early phase of idiopathic myelofibrosis, are discussed. The differentiation is not only of academic interest but has relevant practical implications, since survival in the two conditions is significantly different. The possible significance of an accompanying monoclonal gammopathy is discussed. Copyright 2001 S. Karger AG, Basel
UI - 11454539
AU - Pozzato G; Zorat F; Nascimben F; Comar C; Kikic F; Festini G
TI - Thalidomide therapy in compensated and decompensated myelofibrosis with myeloid metaplasia.
SO - Haematologica 2001 Jul;86(7):772-3
UI - 11548978
AU - Gilbert HS
TI - Diagnosis and treatment of thrombocythemia in myeloproliferative disorders.
SO - Oncology (Huntingt) 2001 Aug;15(8):989-96, 998; discussion 999-1000,1006,1008
AD - Albert Einstein College of Medicine, Bronx, New York, USA. email@example.com
Myeloproliferative disorders originate in the clonal expansion of a transformed pluripotential hematopoietic progenitor cell. This results in a group of syndromes that include polycythemia vera, essential thrombocythemia, chronic myelocytic leukemia, and agnogenic myeloid metaplasia. Diagnostic criteria forpolycythemia vera and essential thrombocythemia were codified by the Polycythemia Vera Study Group in 1967 and 1977. Subsequent modifications include criteria for evidence of clonal proliferation by abnormal bone marrow karyotype and demonstration of erythropoietin-independence of erythropoiesis or reduced serum erythropoietin. Phlebotomy is the mainstay of treatment for polycythemia vera. The defining characteristic of essential thrombocythemia is a sustained elevation of the platelet count above 600,000/microL in an untreated patient. Symptoms and risk factors are the main determinants of treatment options for patients with essential thrombocythemia. High-risk patients are candidates for cytoreduction, whereas lower-risk patients receive either no treatment, low-dose aspirin, or another antithrombotic therapy. The availability of newer nonleukemogenic and megakaryocyte-specific agents warrants a reassessment of current treatment options.
UI - 11698058
AU - Rabbani M; Tabakoff B
TI - Chronic ethanol treatment reduces adenylyl cyclase activity in human erythroleukemia cells.
SO - Eur J Pharmacol 2001 Oct 26;430(1):19-23
AD - Department of Pharmacology, Isfahan University of Medical Sciences, School of Pharmacy, Hezar Jerib Avenue, Isfahan, Iran. firstname.lastname@example.org
Characteristic changes of platelet membrane adenylyl cyclase activity have been described in men with alcoholism. We studied the occurrence of these changes in human erythroleukemia (HEL) cells after chronic ethanol treatment. Chronic treatment of the HEL cell with ethanol (50 or 100 mM) for 48 h resulted in significant reduction of prostaglandin E1-stimulated adenylyl cyclase activity. The acute ethanol (200 mM, 5 min) enhancement of adenylyl cyclase activity was significantly reduced after chronic ethanol treatment. We also observed a reduction in phorbol-12,13-dibutyrate (PDB) enhancement of prostaglandin E1-stimulation after chronic ethanol treatment. Chronic ethanol treatment (50 or 100 mM) reduced the activity of adenylyl cyclase in response to stimulation by acute ethanol to a greater extent than that of after acute PDB. The increase in cAMP formation by ethanol and PDB was only evident when prostaglandin E1 was present and under basal conditions (when no stimulatory agent was present) ethanol up to 200 mM, and PDB up to 1 M, had no significant effect on adenylyl cyclase activity. The reduced capacity of ethanol and/or PDB to stimulate adenylyl cyclase activity after chronic ethanol treatment suggests the involvement of a common denominator in the action of ethanol and PDB.
UI - 11746971
AU - Fioretos T; Panagopoulos I; Lassen C; Swedin A; Billstrom R; Isaksson M;
TI - Strombeck B; Olofsson T; Mitelman F; Johansson B Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.
SO - Genes Chromosomes Cancer 2001 Dec;32(4):302-10
AD - Department of Clinical Genetics, Lund University Hospital, Sweden. Thoas.Fioretos@klingen.lu.se
Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best-studied examples. The fibroblast growth factor receptor 1 (FGFR1) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes-ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27-become fused to the tyrosine kinase domain of FGFR1. These 8p11-translocations are associated with characteristic morphologic and clinical features, referred to as "8p11 MPS." In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1-4 in-frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL, it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation. Copyright 2001 Wiley-Liss, Inc.
UI - 11325659
AU - Gil-Fernandez JJ; Martinez-Chamorro C; Tomas JF
TI - The irreplaceable image: A giant hepatic mass of myeloid metaplasia in a patient without myelofibrosis.
SO - Haematologica 2001 Apr;86(4):445
AD - Hematology Department,Clinica Ruber, Madrid, Spain. email@example.com
UI - 2236481
AU - Pagliuca A; Mufti GJ; Janossa-Tahernia M; Eridani S; Westwood NB;
TI - Thumpston J; Sawyer B; Sturgess R; Williams R In vitro colony culture and chromosomal studies in hepatic and portal vein thrombosis--possible evidence of an occult myeloproliferative state.
SO - Q J Med 1990 Sep;76(281):981-9
AD - Academic Department of Haematological Medicine, King's College Hospital, London.
We have studied the prevalence of an underlying myeloproliferative state in 20 patients with either hepatic or portal vein thrombosis. Using conventional clinical and laboratory criteria, an underlying myeloproliferative state was identified as the cause of the thrombosis in five patients (25%). A further 10 of the remaining 15 cases were found to have characteristic in vitro bone marrow culture studies and cytogenetic abnormalities suggestive of an underlying myeloproliferative disorder. Although none of these 10 cases have developed overt clinical and laboratory features of such a myeloproliferative disorder after a median observation period of two years, the presence of clonal karyotypic abnormalities in three cases, increased megakaryocyte colony growth in three cases and endogenous erythropoietin independent colony growth of the marrow erythroid progenitors in seven cases, argues strongly in favour of a primary haematological disorder. This has important therapeutic implications, particularly in cases being considered for orthotopic liver transplantation.
UI - 2272176
AU - Hyun BH; Gulati GL; Ashton JK
TI - Myeloproliferative disorders. Classification and diagnostic features with special emphasis on chronic myelogenous leukemia and agnogenic myeloid metaplasia.
SO - Clin Lab Med 1990 Dec;10(4):825-38
AD - Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
Leukocytosis, mild anemia, thrombocytosis, and panhyperplasia in the marrow characterize the early stages of most of the CMPD, whereas extramedullary hematopoiesis (such as in the spleen or liver), peripheral cytopenias (anemia, leukopenia, or thrombocytopenia), and myelofibrosis, with or without osteosclerosis, reflect the changes seen in the later stages. Transitions among the different CMPD and termination in acute leukemia or marrow failure also are common. CML often is characterized by leukocytosis and the presence of the entire spectrum of granulocytes (mature and immature) in the blood and marrow, reduced LAP, hypercellularity with prominent granulocytic hyperplasia in the marrow, Ph chromosome, and bcr-abl gene rearrangement. Typical features of AMM include leukoerythroblastosis, teardrop poikilocytosis, anemia, increased or normal LAP, prominent megakaryocytic hyperplasia in the marrow, dyshematopoiesis, and hyperplastic or fibrotic/sclerotic marrow.
UI - 2002687
AU - Diez-Martin JL; Graham DL; Petitt RM; Dewald GW
TI - Chromosome studies in 104 patients with polycythemia vera.
SO - Mayo Clin Proc 1991 Mar;66(3):287-99
AD - Cytogenetics Laboratory, Mayo Clinic, Rochester, MN 55905.
Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy.
UI - 2049740
AU - Ohyashiki K; Sasao I; Ohyashiki JH; Murakami T; Iwabuchi A; Tauchi T;
TI - Saito M; Nakazawa S; Serizawa H; Ebihara Y; et al Clinical and cytogenetic characteristics of myelodysplastic syndromes developing myelofibrosis.
SO - Cancer 1991 Jul 1;68(1):178-83
AD - First Department of Internal Medicine, Tokyo Medical College, Japan.
Myelofibrosis occurs in various hematologic neoplasias, including myelodysplastic syndrome (MDS), with a relatively low incidence. To gain insight into the clinical and cytogenetic implications of MDS patients in whom myelofibrosis develops, statistical analysis was done on 82 primary MDS patients with successful cytogenetic results. Seven patients had myelofibrosis during the course of the disease (8.5%, Group I), 34 had abnormal karyotypes without myelofibrosis (41.5%, Group II), and the other 41 had abnormal karyotypes without myelofibrosis (50%, Group III). All of the MDS patients except one with myelofibrosis had cytogenetic abnormalities, and four of them had multiple chromosome abnormalities. In univariant analysis, MDS patients with myelofibrosis showed no significant differences in age, sex, or peripheral blood data. In contrast, patients with chromosome abnormalities evolved into myelofibrosis with a high incidence compared with those with normal karyotypes (14.6% versus 2.4%, P = 0.054). The occurrence of myelofibrosis was higher during the first 6 months after the diagnosis of MDS than in the next 6 months (6.1% versus 0%, P = 0.045). Most of the MDS patients survived for less than 10 months after myelofibrosis was evident. Furthermore, survival was significantly shorter in Group I compared with Groups II (P less than 0.05) and III (P less than 0.01). Among the MDS patients in whom myelofibrosis developed, some were associated with acute megakaryoblastic leukemia, indicating a heterogeneity of clinical features in MDS with myelofibrosis.
UI - 2065305
AU - Hawkins AL; Miller CB; Burke PJ; Griffin CA
TI - Evolution of a near-triploid karyotype in a secondary erythroleukemia.
SO - Cancer Genet Cytogenet 1991 Jul 1;54(1):11-20
AD - Johns Hopkins Oncology Center, Baltimore, Maryland 21205.
We report a case of erythroleukemia (EL;FAB M6), preceded by a myelodysplastic phase, in a 50-year-old male 8 years after treatment for Hodgkin's lymphoma. Cytogenetic analysis of bone marrow at time of diagnosis of EL revealed three cell lines: 1) 28 of 53 cells (53%) were hypodiploid, 43,XY,-5,-7,-12; 2) 23 of 53 cells (43%) were near-triploid, stemline 67-69,XY,+2,del(5)(q11.2),+del(5)(q11.2),+6,-7,+8,-9,-11,-12,+15,-16,der (17)t (17;?) (p11.2;?),-18,-20,-20,+22,+r, + mar (relative to a complete triploid cell); 3) 2 of 53 cells (4%) were normal 46,XY. The relative monosomies of 5, 7, and 12 in both abnormal lines suggest that the near-triploid line evolved from the hypodiploid line. A single hypodiploid cell with both del(5) and der(17) chromosomes that appeared identical to those in the near-triploid line suggests that polyploidization occurred after these structural rearrangements. While EL is not characterized by any well-defined structural abnormality, reported cases are frequently hypodiploid, with occasional cases of polyploidization, as in our patient, EL in adults without previous neoplasia or recognized mutagenic exposure has been shown to have loss or deletion of chromosomes 5 and 7, also characteristic of myelodysplastic syndromes and secondary leukemia. Our patient had a relative lack of chromosomes 5 and 7 in both abnormal clones, as well as a del(5)(q11) in the near-triploid line. This case of EL clearly demonstrates the evolution of a complex near-triploid line from a hypodiploid line, with chromosome abnormalities typical of both EL and secondary leukemia.
UI - 1854612
AU - Patton WN; Bunce CM; Larkins S; Brown G
TI - Defective erythropoiesis in primary myelofibrosis associated with a chromosome 11 abnormality.
SO - Br J Cancer 1991 Jul;64(1):128-31
AD - Department of Haematology, Medical School, University of Birmingham, UK.
A case of primary myelofibrosis was identified with a previously unreported complex karyotype with two abnormal clones in addition to a proportion of normal cells: 46,XY,-2,-11, + der(2)t(2;11) (q24/31;q13), + mar and 45,XY,-2,-11, + der(2)t(2;11)(q24/31;q13), + mar, -17, del(7q). Study of circulating committed progenitors from this patient consistently showed (1) an absence of erythroid progenitors which is uncommon and (2) greatly increased granulocyte-monocyte progenitors (CFU-GM) which is generally observed in myelofibrosis. Further study showed that peripheral blood mononuclear cells co-cultured with irradiated normal bone marrow stroma generated increased numbers of CFU-GM compared with controls but failed to generate erythroid progenitors, providing evidence for an intrinsic defect in erythropoiesis. Only once previously has the absence of erythroid progenitors in primary myelofibrosis been studied in relation to cytogenetic abnormalities. This case also revealed a complex karyotype which, however, shared with our case a defect on chromosome 11. The identification of two cases of primary myelofibrosis which lack committed erythroid progenitor cells and which show in common a chromosomal defect on chromosome 11 point to the existence of genes on this chromosome which play a key role during erythropoiesis.
UI - 1774954
AU - Rege-Cambrin G; Speleman F; Kerim S; Scaravaglio P; Carozzi F; Dal Cin
TI - P; Michaux JL; Offner F; Saglio G; Van den Berghe H Extra translocation +der(1q9p) is a prognostic indicator in myeloproliferative disorders.
SO - Leukemia 1991 Dec;5(12):1059-63
AD - Dipartimento di Scienze Biomediche e Oncologia Umana, Sezione Clinica, University of Torino, Italy.
An identical extra derivative chromosome resulting from a translocation between the long arm of chromosome 1 and the short arm of chromosome 9, +der(1q9p), has been observed in three patients with a myeloproliferative disorder. Two patients had polycythemia vera in transformation (erythroleukemia in one patient and refractory anemia in the second), whereas the third patient had myelofibrosis which later evolved into acute myelomonocytic leukemia. The two patients who developed overt leukemia did not receive any previous cytotoxic treatment. Non-isotopic in situ hybridization was performed in two patients, allowing for the localization of the breakpoints in 1q12 and 9q12. A similar rearrangement has been previously described in patients with polycythemia vera, either at diagnosis or in advanced stages of the disease. These data suggest that this chromosome abnormality may be consistently associated with myeloproliferative disorders showing a high propensity to transformation, which is not treatment related, and the finding of the +der(1q9p) may represent a poor prognostic sign when observed in the chronic phase.
UI - 1550774
AU - Wang JC; Lang HD; Lichter S; Weinstein M; Benn P
TI - Cytogenetic studies of bone marrow fibroblasts cultured from patients with myelofibrosis and myeloid metaplasia.
SO - Br J Haematol 1992 Feb;80(2):184-8
AD - SUNY Health Science Center, Brookdale Hospital Medical Center, Department of Hematology and Oncology, Brooklyn.
Cytogenetic studies of bone marrow fibroblasts and blood cells from peripheral blood or bone marrow were performed in 19 patients with myelofibrosis with myeloid metaplasia (group 1), nine patients with other myeloproliferative syndromes without myelofibrosis (group 2), and 12 patients with anaemia secondary to iron deficiency or chronic inflammatory disease (group 3). Clonal cell populations with abnormal karyotypes were seen in the bone marrow or blood in five of 14 (36%) group 1 patients, one of nine (11%) group 2 patients and none (0%) of the group 3 patients. Abnormal karyotypes of bone marrow fibroblasts were found in three of 16 (19%) of patients of group 1, and in two of nine (22%) and two of 12 (17%) patients each of groups 2 and 3, respectively. Since abnormal karyotypes can be found in bone marrow fibroblasts cultured from normal subjects, and since the abnormalities seen in the bone marrow fibroblasts differed from those found in bone marrow or blood cells, it is suggested that abnormal karyotypes found in bone marrow fibroblasts cultured from patients with primary myelofibrosis do not necessarily reflect neoplasia. The results of this study are compatible with the widely accepted hypothesis that in patients presenting with 'primary' myelofibrosis, the fibrosis is a secondary reactive process.
UI - 1581880
AU - Jotterand Bellomo M; Parlier V; Muhlematter D; Grob JP; Beris P
TI - Three new cases of chromosome 3 rearrangement in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome.
SO - Cancer Genet Cytogenet 1992 Apr;59(2):138-60
AD - Division de Genetique Medicale, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Defects of 3q in bands q21 and q26 have been reported in more than 70 cases of acute nonlymphocytic leukemia (ANLL), myelodysplastic syndrome (MDS), and myeloproliferative disorder (MPD) in blast crisis. In this paper three additional patients are described: patient 1 with refractory anemia with excess of blasts in transformation (RAEB-T) and inv(3)(q21q26), patient 2 with RAEB-T and t(3;3)(q21;q26), and patient 3 with myelofibrosis with myeloid metaplasia (MMM) in blast crisis and inv(3)(q21q26). In addition to 3q rearrangements, monosomy 7 and del(7)(q22q36) were observed in patients 1 and 2, respectively. In the three patients, the most characteristic clinical features were elevated platelet counts, marked hyperplasia with dysplasia of the megakaryocytes, and poor prognosis. Although disturbance of thrombopoiesis was not systematically observed in all patients with t(3;3)(q21;q26), inv(3)(q21q26), and ins or dup(3)(q21----q26), study of the 77 cases reported and of the three cases presented here brings further evidence to the existence of a cytogenetic syndrome involving bands q21 and q26 simultaneously, which represents a subtype of ANLL, MDS, and MPD, characterized by normal or elevated platelet counts, hyperplasia with dysplasia of megakaryocytes, multilineage involvement, young median age of patients with MDS, preferential involvement of women in t(3;3), high incidence of chromosome 7 defects in MDS and ANLL, short duration of the MDS phase, no response to chemotherapy, short survival, and por prognosis.