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NCI CANCERLIT® Search: Myeloproliferative Disorders - August 2002
National Cancer Institute®
Ultima Vez Modificado: 1 de agosto del 2002
- Osteogenic differentiation of mesenchymal stem cells derived from bone marrow of patients with myeloproliferative disorders.
- Unusually prolonged survival of a case of acute megakaryoblastic leukemia secondary to long-standing polycythemia vera.
- Hydroxyurea-associated platelet count oscillations in polycythemia vera: a report of four new cases and a review.
- Isolated pentasomy of chromosome 8 in erythroleukemia.
- Polycythemia vera: diagnosis and treatment 2002.
- Transient myeloproliferative disorder with a CD7+ and CD56+ myeloid/natural killer cell precursor phenotype in a newborn.
- Erythroleukemia: a need for a new definition.
- Splenectomy in patients with mixed myelodysplastic/myeloproliferative disease.
- The expression pattern of c-mpl in megakaryocytes correlates with thrombotic risk in essential thrombocythemia.
- p53 activation results in rapid dephosphorylation of the eIF4E-binding protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition
Table of Contents
1
UI - 12099203
AU - Lee HS; Tang JL; Chiou LL; Tsai KS; Jiang CC; Yang PC; Yang PM; Huang GT
TI -
Osteogenic differentiation of mesenchymal stem cells derived from bone
marrow of patients with myeloproliferative disorders.
SO - J Formos Med Assoc 2002 Feb;101(2):124-8
AD - Department of Internal Medicine, National Taiwan University Hospital, 7
Chung-Shan South Road, Taipei, Taiwan.
BACKGROUND: It has been frequently reported that culture-expanded
mesenchymal stem cells from bone marrow of healthy donors can be induced
to differentiate to osteocytic lineage. This study examined the
potential for osteogenic differentiation of mesenchymal stem cells
obtained from two patients with myeloproliferative disorders. METHODS:
Mesenchymal stem cells were derived from bone marrow aspirates obtained
in an outpatient clinic from two patients, one with polycythemia vera
and the other with essential thrombocythemia. Nucleated bone marrow
cells were directly cultured in flasks. Adherent fibroblastic cells in
monolayers were isolated by removing nonadherent cells during medium
changes. Osteogenic differentiation was induced in expanded adherent
cells for 2 weeks in osteogenic medium containing 100 nmol/L
dexamethasone, 10 mmol/L beta-glycerophosphate, and 0.05 mmol/L
L-ascorbic acid-2-phosphate. Osteogenic differentiation was evaluated by
alkaline phosphatase staining and determination of calcium in deposited
minerals on culture plates. The expression of osteopontin mRNA was
determined by reverse transcription-polymerase chain reaction. RESULTS:
After induction in osteogenic medium, the expression of alkaline
phosphatase in mesenchymal stem cells became more intense. Induced
alkaline phosphatase-positive cells assumed an irregular shape with
multiple spiculate projections, while uninduced alkaline
phosphatase-positive cells had a flattened polygonal shape or were
elongated. Calcium deposition on the plates of induced cells was 0.39
+/- 0.03 mumol/well in cells from the patient with polycythemia vera and
0.54 +/- 0.03 mumol/well in cells from the patient with essential
thrombocythemia, but was not detectable in uninduced cells from either
patient. Induction by osteogenic medium markedly increased the
expression of osteopontin mRNA in stem cells derived from both patients.
CONCLUSIONS: In this study, mesenchymal stem cells obtained from
aspiration of bone marrow in patients with myeloproliferative disorders
were expanded by culture. After osteogenic induction, these cells were
shown to be able to differentiate into osteocytic lineage in vitro.
2
UI - 12008090
AU - Stamatopoulos K; Yataganas X; Papadaki T; Paterakis G
TI -
Unusually prolonged survival of a case of acute megakaryoblastic
leukemia secondary to long-standing polycythemia vera.
SO - Leuk Res 2002 Jul;26(7):699-700
3
UI - 11911405
AU - Steensma DP; Harrison CN; Tefferi A
TI -
Hydroxyurea-associated platelet count oscillations in polycythemia vera:
a report of four new cases and a review.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1243-53
AD - Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
steensma.david@mayo.edu
Cyclic oscillations in the peripheral blood platelet count were recently
described in two patients with polycythemia vera (PV) receiving therapy
with hydroxyurea (HU). This phenomenon can make proper HU dosing very
challenging and may be especially problematic in PV patients who are at
risk for thrombohemorrhagic complications. In this report, we describe
four new cases of HU-associated platelet oscillations in patients with
PV and extend our observations on one of the two previously reported
cases. We also review cyclic thrombocytosis within the broader context
of periodic hematopoiesis. A thrombopoietin-mediated negative feedback
loop is central to most models of periodic thrombopoiesis, but this is
probably an oversimplification. It is possible that HU destabilizes the
delicate balance of thrombopoietin/c-Mpl signaling in megakaryocytic
lineage hematopoiesis that is already markedly altered in PV; this
hypothesis remains speculative. For patients who develop oscillatory
variation in their platelet counts associated with HU use, keeping the
HU dose constant may result in damping or termination of the cycles.
However, this strategy is not always successful.
4
UI - 11911427
AU - Athanasiadou A; Saloum R; Gaitatzi M; Anagnostopoulos A; Fassas A
TI -
Isolated pentasomy of chromosome 8 in erythroleukemia.
SO - Leuk Lymphoma 2001 Nov-Dec;42(6):1409-12
AD - Department of Haematology, George Papanicolaou General Hospital,
Thessaloniki, Greece.
Pentasomy 8 as a sole anomaly in hematological disorders is rare. Only 2
such cases, one in acute monocytic leukemia and one in chronic
myelomonocytic leukemia have been described in the literature to date.
Here, we report the first case of a 42 year old man with erythroleukemia
displaying a pentasomy 8 clone. Conventional cytogenetics of bone marrow
cells showed 16 metaphases with pentasomy 8 and 9 with normal diploidy.
Fluorescence in situ hybridization (FISH) analysis using a whole
chromosome painting probe and a centromeric probe specific for
chromosome 8 confirmed the presence of pentasomy 8 and also revealed a
low percentage of a trisomic and a tetrasomic clone. The patient died
three days after diagnosis without chemotherapy. The findings suggest
that pentasomy 8 is associated with a heterogeneous group of myeloid
disorders and probably plays a specific role in the progression of
myeloid neoplasia.
5
UI - 12113056
AU - Berlin NI
TI -
Polycythemia vera: diagnosis and treatment 2002.
SO - Expert Rev Anticancer Ther 2002 Jun;2(3):330-6
AD - Sylvester Cancer Center, Department of Medicine, University of Miami,
FL, USA. nberlin@pol.net
Since 1903 when polycythemia vera was designated by Osler as a new
identity the clinical manifestations at the time of
diagnosis--symptomatology, physical and hematological findings have
become well known. Criteria for diagnosis have been established as well
as treatment goals. However, agreement on how best to treat this disease
has eluded the hematologists particularly as our understanding of the
evolution of the hematological findings has become better known. The
hemorrhagic and thrombotic complications and acute leukemia in patients
managed with myelosuppressive regimens have come to the forefront.
Criteria to be used in the comparison of treatment regimens are
suggested from which in this author's opinion the use of 32P becomes the
treatment of choice, but not all will agree.
6
UI - 12142790
AU - Svaldi M; Moroder W; Messner H; Battisti L; Venturi R; Coser P; Mitterer
TI -
M
Transient myeloproliferative disorder with a CD7+ and CD56+
myeloid/natural killer cell precursor phenotype in a newborn.
SO - J Pediatr Hematol Oncol 2002 Jun-Jul;24(5):394-6
AD - Department of Hematology, Regional Hospital Bozen, Bozen, Italy.
Anewborn with a transient myeloproliferative disorder and a
myeloid/natural killer cell leukemia phenotype is described. The blasts
expressed CD7, CD33, CD34, CD56, and CD117 but did not react with
cytoplasmic myeloperoxidase and were negative for cy CD22, HLA-DR, and
CD90 expression. No megakaryoblastic surface markers were identified.
The blast population disappeared from the peripheral blood and bone
marrow within 2 months, but hepatomegaly and recurrent respiratory
insufficiency persisted. The patient died of unilateral pneumonia in the
third month of life. Neither extramedullary infiltration nor other
hematologic signs of disease progression were found.
7
UI - 12145675
AU - Park S; Picard F; Dreyfus F
TI -
Erythroleukemia: a need for a new definition.
SO - Leukemia 2002 Aug;16(8):1399-401
AD - Service d'Hematologie, Hopital Cochin, Paris, France.
The new WHO classification abolishes the frontier between RAEB-t with
20% of blasts and leukemia with 30% of blasts. We review the definitions
of erythroleukemia and discuss the relationship between FAB AML6, RAEB-t
and AML6 variant. We ask whether secondary erythroleukemias are the same
entity as RAEB-t on survival, karyotype and cytologic characteristics.
We suggest that 'AML6 variant' with pure erythroid lineage proliferation
would be the real de novo erythroleukemia. Current FAB AML6 entity will
probably be classified in either subgroup (1) multilineage dysplasia;
(2) therapy-related leukemia; or (3) acute erythroid leukemia subdivided
into erythroleukemia (erythroid/myeloid) and pure erythroid leukemia, in
the WHO classification - a classification which highlights the
importance of clinical and cytogenetic prognostic factors.
8
UI - 12107559
AU - Kraemer D; Rudiger T; Reimer P; Muller-Hermelink HK; Wilhelm M
TI -
Splenectomy in patients with mixed myelodysplastic/myeloproliferative
disease.
SO - Ann Hematol 2002 Jun;81(6):308-11
AD - Medizinische Poliklinik, University Wurzburg, Germany.
d.kraemer@medizin.uni-wuerzburg.de
According to the classification of the World Health Organization, the
designation myelodysplastic/myeloproliferative disorder, unclassifiable
may be applied to cases that have clinical, laboratory, and morphologic
features that support a diagnosis of a myelodysplastic syndrome (MDS) as
well as a myeloproliferative disorder (MPD), but that do not meet the
criteria for any of the other entities included in the MDS/MPD category
[3]. In this paper we report on two Caucasian patients with
unclassifiable myelodysplastic syndromes with proliferative
characteristics. Both patients were suffering from thrombocytopenia and
splenomegaly and underwent splenectomy. The weight of the spleen
specimens was more than 2000 g. Histopathology findings revealed a
marked infiltration of the spleen with extramedullary hematopoiesis.
After surgery, one patient showed a rapid increase of platelets in
peripheral blood and developed severe thrombocytosis. In the other case,
the patient was suffering from a decrease of platelets and died in
hypovolemic shock caused by gastrointestinal bleeding. In summary, these
two cases demonstrate the difficulties of prognosis and treatment in
patients with mixed myelodysplastic/myeloproliferative disorders.
Additionally, we indicate the potential positive outcome of splenectomy
as ultima ratio in patients with these hematological features and severe
thrombopenia.
9
UI - 12091373
AU - Teofili L; Pierconti F; Di Febo A; Maggiano N; Vianelli N; Ascani S;
TI -
Rossi E; Pileri S; Leone G; Larocca LM; De Stefano V
The expression pattern of c-mpl in megakaryocytes correlates with
thrombotic risk in essential thrombocythemia.
SO - Blood 2002 Jul 15;100(2):714-7
AD - Department of Hematology, Catholic University, Rome, Italy.
lteofili@rm.unicatt.it
Using immunohistochemistry, we investigated the expression of c-mpl in
bone marrow megakaryocytes of 88 patients with essential thrombocythemia
(ET), 6 patients with secondary thrombocytosis (ST), and 20 patients
with lymphoma (controls). Considering both the pattern of expression and
the staining intensity, we identified a uniform and a heterogeneous
pattern of c-mpl expression. The uniform pattern was found in all the
controls, all the patients with ST, and 28 of the patients with ET, with
a strong staining intensity observed in most megakaryocytes (> 80%). In
contrast, c-mpl expression was heterogeneous in 60 patients with ET, 18
of whom (30%) presented with thrombosis at diagnosis, a significant
difference from patients with a uniform c-mpl pattern (2 of 28; 7%; P
=.026). In particular, the overrepresentation of thrombotic
complications in patients with a heterogeneous c-mpl expression pattern
was found mainly among patients with a significant percentage (10% to
40%) of weakly stained or c-mpl-negative megakaryocytes
(heterogeneous-weak pattern; 13 of 30; 43%; P =.002). Accordingly, this
pattern was associated with a 6.1-fold increased risk of thrombosis
compared with that of patients with a uniform c-mpl pattern. In
conclusion, the presence of a heterogeneous pattern of c-mpl
distribution in bone marrow megakaryocytes could be a useful diagnostic
criterion in the differential diagnosis of thrombocytosis. Furthermore,
detection of a significant percentage of weakly stained or
c-mpl-negative megakaryocytes can identify patients with a higher risk
of thrombosis.
10
UI - 12149653
AU - Horton LE; Bushell M; Barth-Baus D; Tilleray VJ; Clemens MJ; Hensold JO
TI -
p53 activation results in rapid dephosphorylation of the eIF4E-binding
protein 4E-BP1, inhibition of ribosomal protein S6 kinase and inhibition
of translation initiation.
SO - Oncogene 2002 Aug 8;21(34):5325-34
AD - The Department of Medicine, University/Ireland Cancer Center, Case
Western Reserve University School of Medicine, 10900 Euclid Ave.-BRB
333, Cleveland, Ohio, OH 44106-4937, USA.
p53 is an important regulator of cell cycle progression and apoptosis,
and inactivation of p53 is associated with tumorigenesis. Although p53
exerts many of its effects through regulation of transcription, this
protein is also found in association with ribosomes and several mRNAs
have been identified that are translationally controlled in a
p53-dependent manner. We have utilized murine erythroleukemic cells that
express a temperature-sensitive p53 protein to determine whether p53
also functions at the level of translation. The data presented here
demonstrate that p53 causes a rapid decrease in translation initiation.
Analysis of several potential mechanisms for regulating protein
synthesis shows that p53 has selective effects on the phosphorylation of
the eIF4E-binding protein, 4E-BP1, and the activity of the p70 ribosomal
protein S6 kinase. These data provide evidence that modulation of
translational activity constitutes a further mechanism by which the
growth inhibitory effects of p53 may be mediated.
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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