Association between trisomy 8 and the immunophenotype of blast cells from acute leukemias secondary to a myelodysplastic syndrome or chronic myeloproliferative disorders

1997 ◽  
Vol 74 (5) ◽  
pp. 209-214 ◽  
Author(s):  
M. Garcia-Isidoro ◽  
M. D. Tabernero ◽  
M. L. Najera ◽  
M. C. Lopez-Berges ◽  
A. Martinez ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Myeloproliferative Disorders ◽  
Trisomy 8 ◽  
Acute Leukemias ◽  
Chronic Myeloproliferative Disorders ◽  
Blast Cells

scholarly journals Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics [see comments]

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 768-774
Author(s):  
JF San Miguel ◽  
JM Hernandez ◽  
R Gonzalez-Sarmiento ◽  
M Gonzalez ◽  
I Sanchez ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myelodysplastic Syndrome ◽  
Molecular Genetic ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Acute Leukemias ◽  
Cell Components ◽  
Blast Cells ◽  
Multiparameter Analysis

We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)- beta, -gamma, and -delta and the major breakpoint cluster region [M- bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.

scholarly journals Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics [see comments]

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 768-774 ◽  
Author(s):  
JF San Miguel ◽  
JM Hernandez ◽  
R Gonzalez-Sarmiento ◽  
M Gonzalez ◽  
I Sanchez ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Myelodysplastic Syndrome ◽  
Molecular Genetic ◽  
Cell Receptor ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Acute Leukemias ◽  
Cell Components ◽  
Blast Cells ◽  
Multiparameter Analysis

Abstract We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)- beta, -gamma, and -delta and the major breakpoint cluster region [M- bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.

Megakaryocytes and Platelets as the Main Cause for Vascular Events in Chronic Myeloproliferative Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 151-163 ◽  
Author(s):  
W. Schneider ◽  
A. Wehmeier
Keyword(s):  
Mononuclear Cells ◽  
Buoyant Density ◽  
Myeloproliferative Disorders ◽  
Term Therapy ◽  
Volume Distribution ◽  
Bleeding Tendency ◽  
Vascular Events ◽  
Chronic Myeloproliferative Disorders ◽  
Clonal Hematopoiesis ◽  
Induced Aggregation

SummaryMegakaryocytes are part of clonal hematopoiesis in chronic myeloproliferative disorders and are responsible for most of the clinical complications in this disease. About 30-40% of patients with polycythemia vera (PV) and essential thrombocythemia (ET) suffer from thrombotic complications, and microcirculatory disorders are common. Spontaneous bleeding mainly from the gastrointestinal tract is another complication that is especially prevalent in myelofibrosis and advanced stages of chronic myeloid leukemia.In vivo, the bone marrow is hypercellular and the concentration of megakaryocytes increased with characteristic morphological abnormalities. Megakaryocytes are enlarged and ploidy is increased in PV and ET but small mononuclear cells with decreased ploidy are a feature of CML. Despite spontaneous growth in cul-ture, megakaryocytes in chronic MPD are hypersensitive to added interleukin-3, interleukin-6 and GM-CSF.Platelets released from these megakaryocytes show abnormal morphology and ultrastructure, reflected in loss of storage granules and organelles, increased volume distribution and low buoyant density. Uptake, storage and secretion of platelet dense granule constituents is abnormal, and the plasma levels of platelet specific proteins which may also include growth factors for fibroblasts are elevated. At high platelet counts, spontaneous aggregation is observed, whereas agonist-induced aggregation in vitro with adrenaline, ADP and collagen is often defective. Platelet thromboxane generation may be stimulated, and production along the lipoxygenase pathway is decreased. Abnormalities of glycoprotein receptors and decreased fibrinogen binding have been reported but their clinical significance is uncertain. Several observations suggest that not only receptor defects but ineffective intracellular signalling may be responsible for platelet function abnormalities.No single underlying defect has been discovered that could explain this variety of pathological findings. Moreover, a combination of intrinsic megakaryocyte abnormalities and increased susceptibility of platelets to activation makes it difficult to differentiate secondary phenomena from effects of clonal hematopoiesis. How-ever, there are some clinical guidelines for therapy.Most elderly patients will be treated with cytoreductive therapy. Alkylating drugs and 32P have been shown to be leukemogenic, but even hydroxyurea may have a 10% incidence of leukemia induction after long-term therapy. Therapy with platelet-inhibitory drugs is often not sufficient to control thrombosis, and may aggravate a bleeding tendency, so that younger patients with PV and ET are increasingly treated with anagrelide or interferon alpha (A-IFN). Anagrelide is a quinazolin derivative that specifically inhibits megakaryocytopoiesis, while A-IFN may suppress clonal hematopoiesis by an unknown mechanism.

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