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Abramson Cancer Center
NCI CANCERLIT® Search: Myeloproliferative Disorders - September 2002
National Cancer Institute®
Last Modified: September 1, 2002
- A molecular star in the wars against cancer.
- Red cell mass, spleen size and plasma erythropoietin in polycythaemia vera and apparent polycythaemia.
- Patients with essential thrombocythaemia have an increased prevalence of antiphospholipid antibodies which may be associated with thrombosis.
- Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived
- Melphalan treatment in patients with myelofibrosis with myeloid metaplasia.
- Two groups of chronic myelomonocytic leukaemia: myelodysplastic and myeloproliferative. Prognostic implications in a series of a single
- Current treatment practice for essential thrombocythaemia in adults.
- Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome.
- Products of the TAL1 oncogene: basic helix-loop-helix proteins phosphorylated at serine residues.
- A variant form of acute promyelocytic leukemia with marked myelofibrosis.
- Clearance of erythrocyte allo-antibodies using Rituximab.
- Clinical efficacy and antiangiogenic activity of thalidomide in myelofibrosis with myeloid metaplasia. A pilot study.
- Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant megakaryocytopoiesis.
- Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome.
- [Aplastic myelosis and subsequent leukopenic leukemia, caused by benzene. 1945]
Table of Contents
1
UI - 12181399
AU - Schwartz R
TI -
A molecular star in the wars against cancer.
SO - N Engl J Med 2002 Aug 15;347(7):462-3
2
UI - 12145459
AU - Johansson P; Safai-Kutti S; Lindstedt G; Suurkula M; Kutti J
TI -
Red cell mass, spleen size and plasma erythropoietin in polycythaemia
vera and apparent polycythaemia.
SO - Acta Haematol 2002;108(1):1-7
AD - Hematology Section, Department of Medicine, Sahlgrenska University
Hospital, Goteborg, Sweden.
Most frequently, an elevated packed cell volume (PCV) value arouses the
suspicion of a polycythaemic state. The aim of the present work was to
assess a few readily available variables which could help the clinician
to differentiate between polycythaemia vera (PV) and apparent
polycythaemia (AP). During a 5-year period, 31 consecutive newly
diagnosed patients with PV were identified, and during a 4-year period
38 consecutive subjects were considered to be afflicted with AP. In each
subject: (i) the red cell mass (RCM) and plasma volume were measured,
(ii) the spleen size was assessed using gamma-camera imaging, and (iii)
the plasma erythropoietin (EPO) concentration was determined. The
diagnosis of PV was based upon recently proposed criteria. By
definition, all PV patients had absolute erythrocytosis, i.e. the RCM
was greater than 25% above the mean normal predicted value for the
individual. There was no statistical difference between the plasma
volumes for PV and AP patients. However, the mean measured/predicted
plasma volume for subjects with AP was significantly lower than the mean
for PV. The means for spleen scan areas (posterior and left lateral
projections) for AP patients were identical to the mean reference values
for our laboratory. As compared to AP, in PV the spleen scan areas were
significantly increased, and the lateral spleen scan area was
significantly larger than the posterior area. It was also shown that, in
contrast to AP, both spleen scan areas were significantly larger in male
than in female PV patients. All PV patients had plasma EPO
concentrations below the lower reference limit, and in 68% of the
patients undetectable EPO concentrations were present. Most AP patients
(84%) had EPO values within the reference range; 8% had slightly
subnormal, but not undetectable, plasma EPO levels. Copyright 2002 S.
Karger AG, Basel
3
UI - 12038780
AU - Harrison CN; Donohoe S; Carr P; Dave M; Mackie I; Machin SJ
TI -
Patients with essential thrombocythaemia have an increased prevalence of
antiphospholipid antibodies which may be associated with thrombosis.
SO - Thromb Haemost 2002 May;87(5):802-7
AD - Department of Haematology, University College London Hospital, UK.
claire.harrison@gstt.sthames.nhs.uk
A significant proportion of patients with Essential Thrombocythaemia
(ET) have thrombotic complications which have an important impact upon
the quality, and duration of their life. We performed a retrospective
cross sectional study of the prevalence of antiphospholipid antibodies
(APA) in 68 ET patients. Compared to 200 "elderly" controls (>50 years)
there was a significant increase in anticardiolipin IgM (p < 0.0001) and
anti beta2 glycoprotein I (anti-beta2GPI) IgM (p < 0.0001) antibodies in
ET. Thrombosis occurred in 10/20 with APA and 12/48 without, p = 0.04,
relative risk 2.0 (95% confidence intervals 1.03-3.86): these patients
did not differ in terms of other clinical features. The prevalence of
thrombosis in patients with dual APA (6/7) was significant when compared
to those with single APA (p = 0.02) and the remaining patients (p <
0.0002). Also anti-beta2GP1 IgM antibodies either alone, or in
combination with another APA, were associated with thrombosis (p =
0.02). These results suggest that the prevalence of APA in ET and their
influence upon thrombotic risk merit investigation in a larger study.
4
UI - 12181402
AU - Apperley JF; Gardembas M; Melo JV; Russell-Jones R; Bain BJ; Baxter EJ;
TI -
Chase A; Chessells JM; Colombat M; Dearden CE; Dimitrijevic S; Mahon FX;
Marin D; Nikolova Z; Olavarria E; Silberman S; Schultheis B; Cross NC;
Goldman JM
Response to imatinib mesylate in patients with chronic
myeloproliferative diseases with rearrangements of the platelet-derived
growth factor receptor beta.
SO - N Engl J Med 2002 Aug 15;347(7):481-7
AD - Department of Haematology, Faculty of Medicine, Imperial College,
Hammersmith Hospital, London, United Kingdom. j.apperley@ic.ac.uk
BACKGROUND: A small proportion of patients with chronic
myeloproliferative diseases have constitutive activation of the gene for
platelet-derived growth factor receptor beta (PDGFRB), which encodes a
receptor tyrosine kinase. The gene is located on chromosome 5q33, and
the activation is usually caused by a t(5;12)(q33;p13) translocation
associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase
inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT
kinases and has impressive clinical efficacy in BCR-ABL-positive chronic
myeloid leukemia. METHODS: We treated four patients who had chronic
myeloproliferative diseases and chromosomal translocations involving
5q33 with imatinib mesylate (400 mg daily). Three of the four patients
presented with leukocytosis and eosinophilia; their leukemia cells
carried the ETV6-PDGFRB fusion gene. The fourth patient had
leukocytosis, eosinophilia, and a t(5;12) translocation involving PDGFRB
and an unknown partner gene; he also had extensive raised, ulcerated
skin lesions that had been present for a long time. RESULTS: In all four
patients, a normal blood count was achieved within four weeks after
treatment began. In the patient with skin disease, the lesions began to
resolve shortly after treatment began. The t(5;12) translocation was
undetectable by 12 weeks in three patients and by 36 weeks in the fourth
patient. In the three patients with the ETV6-PDGFRB fusion gene, the
transcript level decreased, and in one patient, it became undetectable
by 36 weeks. All responses were durable at 9 to 12 months of follow-up.
CONCLUSIONS: Imatinib mesylate induces durable responses in patients
with chronic myeloproliferative diseases associated with activation of
PDGFRB. Copyright 2002 Massachusetts Medical Society
5
UI - 11849213
AU - Petti MC; Latagliata R; Spadea T; Spadea A; Montefusco E; Aloe Spiriti
TI -
MA; Avvisati G; Breccia M; Pescarmona E; Mandelli F
Melphalan treatment in patients with myelofibrosis with myeloid
metaplasia.
SO - Br J Haematol 2002 Mar;116(3):576-81
AD - Ematologia, Istituto Regina Elena, Rome, Italy. rob.lati@libero.it
symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic
enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl
and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0
x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate
the efficacy and toxicity of this approach. Among 99 evaluable patients,
66 (66.7%) achieved a response after a median time of 6.7 months: 26
(26.3%) had a normalization of all clinical and haematological
parameters (complete response, CR) and 40 (40.4%) showed an improvement
>50% (partial response, PR). Thirty-three patients (33.3%) were
resistant. Reversible haematological toxicity was the most common
complication. Median durations of CR and PR were 28.4 and 26 months
respectively: median survival of CR + PR patients was 71.2 months
(95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the
non-responders (log-rank test, P =0.002). In the multivariate analysis,
the following variables were significantly associated with a shorter
survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR
= 2.4) and not achieving any type of response, either partial or
complete (HR = 3.9). In conclusion, Melphalan could be a promising
first-line option for MMM patients with clinical or haematological
symptoms requiring treatment.
6
UI - 12127557
AU - Gonzalez-Medina I; Bueno J; Torrequebrada A; Lopez A; Vallespi T;
TI -
Massague I
Two groups of chronic myelomonocytic leukaemia: myelodysplastic and
myeloproliferative. Prognostic implications in a series of a single
center.
SO - Leuk Res 2002 Sep;26(9):821-4
AD - Servicio de Hematologia Clinica, Hospital General Vall d'Hebron, Po Vall
d'Hebron 119-129, Barcelona, Spain. jabueno@hg.vhebron.es
The clinical records of 70 patients seen at our hospital between 1976
and 1998 and diagnosed as suffering from chronic myelomonocytic
leukaemia (CMML) were reviewed in order to confirm the validity of the
classification into two forms of disease that the
French-American-British Co-operative Leukaemia Group (FAB) proposed in
1994: myelodysplastic (MD) and myeloproliferative (MP), depending on the
peripheral white blood cell count (WBC) (less or more than 13 x 10(9)/l,
respectively). After the rejection of incomplete records and lost to
follow up patients, our study population consisted of 49 records. Our
results confirm that, even though this classification is useful in order
to separate two classes of patients, it is not enough to predict the
prognosis in an accurate manner. A lot of studies have tried to find
some prognostic factors, but the results have been discordant. The
multivariate analysis of our group of patients showed three prognostic
factors: serum lactate dehydrogenase (LDH) >1.5 times normal level,
blasts in bone marrow >5%, and peripheral blood leukocytes >10 x
10(9)/l. A second multivariate analysis led us to distinguish two
groups: high risk (2-3 risk factors) and low risk (0-1 risk factors)
(median survival 7 and 44 months, respectively) with a very high
statistic significance (P<0.0001). This score should be applied to other
series of CMML patients in order to confirm its validity.
7
UI - 11336593
AU - Griesshammer M; Bangerter M; Grunewald M
TI -
Current treatment practice for essential thrombocythaemia in adults.
SO - Expert Opin Pharmacother 2001 Mar;2(3):385-93
AD - Department of Medicine III, Robert-Koch-Strasse 8, D-89081 Ulm, Federal
Republic of Germany. martin.griesshammer@medizin.uni-ulm.de
Essential thrombocythaemia (ET) is a relatively benign chronic
myeloproliferative disorder that occurs primarily in middle-aged
patients. Its clinical course is characterised by thomboembolic and,
less frequently, by haemorrhagic complications. Life expectancy of ET is
generally of normal length and progression to acute leukaemia is a rare
event. About one third of all patients are asymptomatic at diagnosis and
many of them remain without complications for years. Therefore, the main
challenge for treating patients with ET is to select patients who will
benefit from a cytoreductive or antiplatelet therapy, because it is
doubtful whether the beneficial effects of therapy outweigh the
potential hazards in all cases. For this reason a risk stratification in
high and low risk ET patients is essential. The treatment of ET has
evolved from alkylating agents to hydroxyurea (HU) or pipobroman and
more recently to agents such as IFN-alpha and anagrelide. Aspirin as an
antiplatelet therapy is also expected to play a part in the treatment of
ET. HU is first-line therapy for elderly patients with high risk ET. In
young ET patients without ET related complications and a platelet count
<< 1000 - 1500 x 10(9)/l abstention from cytoreductive therapy or
therapy with low-dose aspirin alone seems to be appropriate. The aim of
this review is to address the current treatment practice for ET in
adults.
8
UI - 11794699
AU - Yamada S; Hongo T; Okada S; Watanabe C; Fujii Y; Hori H; Yazaki M;
TI -
Hanada R; Horikoshi Y
Distinctive multidrug sensitivity and outcome of acute erythroblastic
and megakaryoblastic leukemia in children with Down syndrome.
SO - Int J Hematol 2001 Dec;74(4):428-36
AD - Department of Pediatrics, Hamamatsu University School of Medicine,
Hamamatsu, Japan.
We assessed the in vitro chemosensitivity of acute erythroblastic and
megakaryoblastic leukemia cells from children with Down syndrome (DS)
compared to non-DS children. We conducted in vitro tests using the MTT
assay of bone marrow samples from 12 children with DS and 16 children
without DS. Patients were newly diagnosed based on the morphology and
expression of platelet-specific antigens. Induction failure occurred
more frequently in the non-DS group (n = 4) than in the DS group (n = 0,
P = .053). Children with DS had a superior event-free survival (EFS)
probability of 0.750 at 4 years, compared to an EFS probability of 0.375
for non-DS children (P = .049). Blast cells from DS patients were
significantly more sensitive to daunorubicin, melphalan, mitoxantrone,
4-hydroperoxy-cyclophosphamide, vincristine, etoposide, bleomycin, and
pirarubicin than those from non-DS patients. Four of the 16 non-DS
patients were found to have acquired an extra chromosome 21 in their
leukemia cells: blasts from these patients also tended to have greater
chemosensitivity than those from patients without an extra chromosome
21. Blast cells from DS patients are markedly sensitive to various
drugs. These results suggest that the fragility of blast cells derived
from DS patients may be related to an increased susceptibility to
apoptosis.
9
UI - 8437851
AU - Cheng JT; Hsu HL; Hwang LY; Baer R
TI -
Products of the TAL1 oncogene: basic helix-loop-helix proteins
phosphorylated at serine residues.
SO - Oncogene 1993 Mar;8(3):677-83
AD - Department of Microbiology, University of Texas, Dallas 75235.
TAL1 gene rearrangement is observed in nearly 30% of patients with
T-cell acute lymphoblastic leukemia (T-ALL), and thus it represents the
most common genetic lesion associated with this disease. Nevertheless,
the presence of TAL1 gene products in normal or leukemic cells has not
been reported. Therefore, immunoprecipitation with anti-TAL1 antisera
was used to demonstrate the presence of TAL1 phosphoproteins, pp42TAL1
and pp22TAL1, in both T-ALL and erythroleukemia cell lines. The pp42TAL1
and pp22TAL1 proteins appear to be phosphorylated forms of full-length
and truncated TAL1 gene products respectively. Phosphoamino acid
analysis revealed that pp42TAL1 contains phosphoserine residues. The
TAL1 phosphoproteins were detected in all of the T-ALL cell lines that
harbor obvious TAL1 gene rearrangements. Interestingly, pp42TAL1 and
pp22TAL1 were also present in some, but not all, of the T-ALL lines
without detectable TAL1 gene alterations. Therefore, TAL1 activation may
promote leukemogenesis in a far greater proportion of T-ALL patients
than the 30% that bear gross TAL1 gene rearrangements.
10
UI - 11721970
AU - Fukuno K; Tsurumi H; Yoshikawa T; Yamada T; Oyama M; Moriwaki H
TI -
A variant form of acute promyelocytic leukemia with marked
myelofibrosis.
SO - Int J Hematol 2001 Oct;74(3):322-6
AD - Department of Internal Medicine, Kisogawa Hospital, Aichi, Japan.
We describe a variant form, French-American-British (FAB) M3v, of acute
promyelocytic leukemia (APL; FAB M3) with atypical morphocytochemical
features, immature antigens (CD34 and HLA-DR) and marked myelofibrosis
(MF). Usual APL cells do not express CD34 or HLA-DR antigens. MF may be
more frequently observed in patients with M3v expressing CD34 and HLA-DR
antigens than in patients with M3 lacking these antigens. Despite marked
MF, recovery from the hypoplastic phase in the case we described was not
delayed after remission induction chemotherapy consisting of
enocitabine, 200 mg/mi2 intravenously; 6-mercaptopurine, 70 mg/m2 orally
for 10 days; daunorubicin 40 mg/m2 intravenously for 4 days; and
all-trans retinoic acid 45 mg/M2 orally between days 20 and 33. The
promyelocytic leukemia-retinoic-acid receptor (PML-RAR) alpha fusion
transcript, according to reverse transcriptase-polymerase chain reaction
(RT-PCR), became negative in the bone marrow after the first course of
consolidation chemotherapy. Autologous peripheral blood stem cell
transplantation (autoPBSCT) was carried out after 3 courses of
consolidation chemotherapy. There were no specific complications based
on MF throughout the clinical course, including engraftment in
autoPBSCT. The patient has been without MF and in molecular remission,
defined as disappearance of the PML-RAR alpha fusion transcript
according to RT-PCR, for 21 months. Longer follow-up will clarify the
effects of autoPBSCT on prognosis in APL with MF.
11
UI - 11979318
AU - Gryn J; Zeigler ZR; Shadduck RK; Thomas C
TI -
Clearance of erythrocyte allo-antibodies using Rituximab.
SO - Bone Marrow Transplant 2002 Apr;29(7):631-2
12
UI - 12200671
AU - Piccaluga PP; Visani G; Pileri SA; Ascani S; Grafone T; Isidori A;
TI -
Malagola M; Finelli C; Martinelli G; Ricci P; Baccarani M; Tura S
Clinical efficacy and antiangiogenic activity of thalidomide in
myelofibrosis with myeloid metaplasia. A pilot study.
SO - Leukemia 2002 Sep;16(9):1609-14
AD - Institute of Hematology and Clinical Oncology 'L e A Seragnoli',
University of Bologna, Italy.
Increased neoangiogenesis has been reported in myelofibrosis with
myeloid metaplasia (MMM). Thus we studied the effects of thalidomide, an
antiangiogenic drug, in 12 MMM patients. Before treatment, all the cases
showed a significantly increased micro-vessel density (MVD); in all
eight tested cases bFGF and VEGF plasma levels were higher than
controls. All patients presented disease progression in the last 3
months with standard therapy, regarding splenomegaly, anemia and/or
thrombocytopenia and/or hyperleukocytosis. Thalidomide was administered
at daily doses increasing from 100 to 600 mg. Eleven out of 12 patients
were evaluable. No progression of disease was seen during the treatment
in any case. In particular, spleen size decreased in 7/11 patients,
anemia improved in 3/4 (two are now transfusion independent),
thrombocytopenia in 2/2 and hyperleukocytosis in 2/5 patients.
Side-effects were frequent, although not severe. After treatment, VEGF
and bFGF plasma levels varied widely and in selected cases decreased. In
particular, VEGF and/or bFGF decreased in 4/5 responders and in 1/3
non-responders. Moreover, MVD significantly decreased in all the
responders evaluated after treatment. We conclude that thalidomide is a
feasible therapy in MMM patients and looks promising at least to control
the growth progression of disease.
13
UI - 12200693
AU - Catani L; Vianelli N; Amabile M; Pattacini L; Valdre L; Fagioli ME; Poli
TI -
M; Gugliotta L; Moi P; Marini MG; Martinelli G; Tura S; Baccarani M
Nuclear factor-erythroid 2 (NF-E2) expression in normal and malignant
megakaryocytopoiesis.
SO - Leukemia 2002 Sep;16(9):1773-81
AD - Istituto di Ematologia e Oncologia Medica 'L. e A. Seragnoli',
University of Bologna, Bologna, Italy.
Although the transcription factor nuclear factor-erythroid 2 (NF-E2) is
known to be functionally linked to the megakaryocytic lineage, little is
known about its role in malignant megakaryocytes. We used real-time
RT-PCR and Western blotting to investigate expression of NF-E2 and its
partner, MafG, in CD34-derived normal (five cases) and malignant
megakaryocytes from essential thrombocythemia (ET) patients (eight
cases) and in megakaryoblastic cell lines. We also quantitated the mRNA
of the thromboxane synthase (TXS) gene, which is directly regulated by
NF-E2. Although real-time RT-PCR showed that both a and f NF-E2 isoforms
were significantly reduced with respect to the normal counterpart both
in ET megakaryocytes and in cell lines (P < or = 0.01), western blotting
revealed decreased NF-E2 protein expression only in the latter. However,
both the NF-E2a/MafG mRNA ratio (P < or = 0.01) and TXS (P< or = 0.01)
mRNA expression were significantly reduced in megakaryocytes from ET
patients and cell lines with respect to healthy subjects. These two
findings provide strong indirect evidence of altered activity of the a
isoform of NF-E2 in malignant megakaryocytes, raising the possibility
that NF-E2 could play a role in megakaryocyte transformation.
14
UI - 12200707
AU - Taketani T; Taki T; Takita J; Ono R; Horikoshi Y; Kaneko Y; Sako M;
TI -
Hanada R; Hongo T; Hayashi Y
Mutation of the AML1/RUNX1 gene in a transient myeloproliferative
disorder patient with Down syndrome.
SO - Leukemia 2002 Sep;16(9):1866-7
15
UI - 11899923
AU - Saita G
TI -
[Aplastic myelosis and subsequent leukopenic leukemia, caused by
benzene. 1945]
SO - Med Lav 2001 Nov-Dec;92(6):373-6
The above citations and abstracts reflect those newly added to CANCERLIT for the month and topic listed in the title. The citations have been retrieved from CANCERLIT using a predefined search strategy of indexed subject terms. Although the search strategy has been refined as best as possible, citations may appear that are not directly related to the topic, and occasionally relevant references may be omitted.
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