1/28. Translocation (4;15)(p16;q24): a novel reciprocal translocation in a patient with BCR/ABL negative myeloproliferative syndrome progressing to blastic phase.A patient with BCR/ABL negative myeloproliferative syndrome with a 46,XY,del(3)(q21), t(4;15)(p16;q24) karyotype is described. fluorescence in situ hybridization performed with chromosomes 4 and 15 painting probes confirmed a novel reciprocal (4;15) translocation. The absence of crkl tyrosine phosphorylation, no activation of the abl kinase as measured by autophosphorylation, and a normal-size abl transcript suggest an alternative mechanism for leukemogenesis to that operative in Ph positive BCR/ABL positive chronic myeloid leukemia. A number of genes potentially relevant to tumorigenesis, some involving the ras signaling pathway, map to the 4p16 and 15q24 chromosome regions.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
2/28. A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): a Japanese case.A 40-year-old male patient presented with leukocytosis and mild splenomegaly. Bone marrow aspirate showed myeloid hyperplasia and eosinophilia resembling chronic myelogenous leukemia in the chronic phase. Cytogenetic examination of bone marrow cells revealed an unusual karyotype, t(8;13)(p11;q12), in 20/20 metaphases. Not the BCR/ABL, but the ZNF198/FGFR1 chimeric mRNA was detected by reverse transcription-polymerase chain reaction. Since 1992, 12 patients with a similar atypical myeloproliferative disorder with T-cell non-Hodgkin's lymphoma or eosinophilia, associated with a t(8;13) translocation in both bone marrow and lymph node specimens, have been described. The present case is an additional one that should be classified into this new clinicopathologic entity.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
3/28. Transient myeloproliferative disorder with erythroid differentiation in down syndrome.A newborn with a karyotype of 47, XY, 21 presented at birth with a white blood cell count of 27 700/microL of which 61% were blast cells. The blast cell morphologic structure was initially not characteristic of any particular lineage, although the cytoplasm contained fine granules and occasional small vacuoles. Routine cytochemical stains were negative, except one for nonspecific esterase that was faintly positive in most of the blast cells. Flow cytometric analyses showed that the blast cells expressed glycophorin A with a subset dimly coexpressing CD45 and were negative for CD34, CD71, myeloid, lymphoid, and platelet-associated antigens. These immunophenotypic findings were consistent with an abnormal erythroid phenotype. A few days postpartum, markedly dysplastic erythroid precursor cells appeared in the peripheral blood and increased in number as the early blast cells decreased. After a period of subdued blast cell production, a second wave of increase in the number of blast cells and dysplastic erythroblasts followed and ended with the disappearance of circulating abnormal cells. The child is now 5 years old and no major illness has been reported since the remission of this disorder. This case most likely belongs to the category of transient myeloproliferative disorders, although the erythroid-like phenotype of blast cells and the evidence of single-lineage maturation to circulating dysplastic erythroid precursors allow the suggestion that this process could represent a special form of a self-limited hematologic disorder in down syndrome.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
4/28. Acute megakaryoblastic leukemia after transient myeloproliferative disorder with clonal karyotype evolution in a phenotypically normal neonate.We report a case of transient myeloproliferative disorder (TMD) in a neonate without features of down syndrome (DS) with clonal karyotype evolution, after apparent spontaneous resolution of TMD, but eventually progressing to acute megakaryoblastic leukemia (AMKL). The patient had petechiae, thrombocytopenia, and blastemia. trisomy 21 with a satellited y chromosome (Yqs) was found in proliferating blasts. A stimulated peripheral blood culture confirmed the constitutional origin of the Yqs, but did not reveal the presence of any trisomic 21 cell. By the age of 3 months, clonal chromosome evolution in the form of an interstitial deletion of the long-arm of chromosome 13 [del(13)(q13q31)] was detected along with trisomy 21 in unstimulated bone marrow cultures. However, remission was achieved without treatment at the age of 4 months. trisomy 21 and del(13)(q13q31) were not identified in either cytogenetics or fluorescence in situ hybridization studies at that time. The child was asymptomatic until the age of 20 months when anemia and thrombocytopenia prompted a bone marrow biopsy, revealing changes consistent with AMKL. The remission proceeded by clonal karyotype evolution in a neonate with TMD demonstrates that clonal karyotype evolution does not indicate an immediately progressive disease. However, the development of AMKL after TMD in this case illustrates the increased risk for leukemia in TMD cases, even without DS. The gradual clonal evolution of the blasts in our patient suggests that "multiple hits" oncogenesis applies to TMD progression to acute leukemia.- - - - - - - - - - ranking = 7keywords = karyotype (Clic here for more details about this article) |
5/28. Abnormalities of chromosome 1 in myeloproliferative disorders.Three patients with myeloproliferative disorders showed a similar chromosome abnormality, accompanied by other abnormalities that were different in each case. Marrow cells from all three patients were trisomic either for the entire chromosome 1 or for its long arm. Patient 1 had a brief period of anemia and thrombocytopenia which preceded a terminal acute leukemia; Patient 2 had polycythemia vera (P.V.) that terminated in acute leukemia; and Patient 3 has P.V. The detection of an abnormal karyotype in patients 1 and 2 was an important factor in establishing the diagnosis of acute leukemia. Preliminary evidence supports the suggestion that some chromosomal changes are nonrandom in myeloproliferative diseases. Nonrandom abnormalities involving the same chromosome have been observed in several human neoplastic disorders.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
6/28. Pure red cell aplasia developing into myeloproliferation with myelodysplasia and subsequent leukemia after cyclosporin A therapy.We describe a very rare case of a patient who presented with red cell aplasia that later developed into myeloproliferation with myelodysplasia and eventually leukemia. A 63-year-old man presented with anemia and reticulocytopenia in May 1997. A bone marrow examination revealed erythroid aplasia with normal production of myeloid cells and megakaryocytes with a normal karyotype. After the diagnosis of pure red cell aplasia was made, the patient was treated with prednisolone and then with cyclosporin A (CyA). Two weeks after the initiation of CyA treatment, the peripheral reticulocyte count began to increase with a regrowth of erythroid cells in the bone marrow. Meanwhile, the peripheral white blood cell and platelet counts also increased to more than 10,000/microL and 1,000,000/microL, respectively. Examination of a bone marrow aspirate in December 1997 revealed myelodysplastic changes with trisomy 8. Despite the discontinuation of CyA and the administration of 1-beta-D-arabinofuranosylcytosine stearyl monophosphate, leukemia developed in August 1998. In September 1998, the patient died of sepsis during a neutropenic period that followed remission-induction therapy. In the mechanism of pathogenesis, CyA may induce upon pure red cell aplasia a secondary myeloproliferative disorder with myelodysplasia and leukemia. An alternative possibility is that CyA reduces autoimmune-mediated suppression of the underlying stem cell disorder and that the result of this reduction is the manifestation of myeloproliferation and leukemia.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
7/28. Transplant decision-making strategies in the myeloproliferative disorders.Myelofibrosis with myeloid metaplasia, also known as idiopathic myelofibrosis (IF) or agnogenic myeloid metaplasia, is one of the characteristic manifestations of polycythemia vera (PV) in the spent phase, and has a particularly adverse prognosis. IF may also present de novo. To date, treatment strategies for both spent-phase PV and IF have frustrated both clinicians and patients, with little clear progress made over the past 50 years. Treatment modalities with some benefit in chronic myeloid leukemia (CML), such as interferon (IFN), have been used to shrink the massive organomegaly seen in these patients and to improve their marrow function, but are not curative, and not all patients respond or can tolerate the agent. A curative approach is allogeneic peripheral hematopoietic stem cell transplantation. The preparative regimens used in fully ablative techniques rule out older patients for consideration, and many younger patients with good prognostic criteria may do sufficiently well on medical treatment or observation to avoid transplantation. Older patients may have the option to undergo a human leukocyte antigen (HLA)-identical sibling transplant using a reduced intensity preparative regimen in order to minimize peritransplant mortality. Thus a prerequisite to the broad use of transplantation is objective determination of candidacy. Several evaluation methods agree that anemia, age, and cytogenetic abnormalities all predict poor survival in IF, suggesting that patients with anemia and an abnormal karyotype are the prime candidates for allogeneic transplantation. Experimental peripheral blood models that may reflect the degree of marrow fibrosis, such as the serum procollagen 3 peptide assay, have been used to determine if they are more informative of patient status than a single, random bone marrow sampling. Marrow fibrosis may be patchy, and thus a marrow biopsy alone without other data about marrow function may be misleading. Considerable long-term success in eradicating fibrosis and restoring normal cytogenetics, normal bone marrow morphology, and normal complete blood cell counts through transplantation has been reported. Many questions remain to be answered, however, before the appropriate role of hematopoietic stem cell transplantation in the setting of both spent-phase PV and IF can be determined.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
8/28. Mixed myelodysplastic syndrome and myeloproliferative disorder with bone marrow and pulmonary fibrosis: the role of megakaryocytes.The case of an 80-year-old woman displaying myelodysplastic syndrome evolving into a myeloproliferative disorder with myelofibrosis and pulmonary fibrosis, is reported. This case is characterized by an initial presentation of a myelodysplastic syndrome with normal karyotype and moderate fibrosis, its evolution towards a myeloproliferative disorder with myelofibrosis and the worsening of pulmonary fibrosis in parallel to the acceleration of the myeloproliferative disorder and myelofibrosis. These features and the high concentration of plasma platelet factor-4 suggest a role of megakaryocyte/platelet degranulation in the development of fibrosis.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
9/28. A biphenotypic transformation of 8p11 myeloproliferative syndrome with CEP1/FGFR1 fusion gene.We describe here the first case of 8p11 myeloproliferative syndrome (EMS) with t(8;9)(p11;q33), who unusually demonstrated B-lymphoblastic/monoblastic biphenotypic transformation. A 57-year-old woman was admitted because of leukocytosis and diagnosed as EMS. Bone marrow was infiltrated with myeloperoxidase (MPO)-, CD10 , CD19 , CD20 , CD34 , HLA-DR small lymphoblasts and MPO , CD2 , CD4 , CD13 , CD14 , CD33 , HLA-DR large monoblasts. The karyotype was 46,XX,t(8;9)(p11;q33)[20] and the CEP1/FGFR1 fusion transcript between CEP1 exon 38 and FGFR1 exon 9 was detected. This case clearly indicates that the blastic transformation in EMS with t(8;9) could arise in the stem cells, which differentiate into not only myelomonocytic but also B-lymphocytic lineages.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
10/28. Two additional cases of isochromosome 21q or translocation 21q21q in hematological malignancies.We report on 2 patients with isochromosome 21q [i(21q)] or translocation 21q21q [t(21q21q)] in myeloid disorders. Of 18 available cases of i(21q) or t(21q21q), 15 were found in myeloid malignancies, often secondary to a previous carcinogen exposure. Complex karyotypes were found in most cases. Four cases presented with i(21q) or t(21q21q) as the sole anomaly, and this might represent a specific entity.- - - - - - - - - - ranking = 1keywords = karyotype (Clic here for more details about this article) |
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