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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The translocation t(6;9)(p23;q34) is detected infrequently in subtypes of haematological malignancies including acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Although the t(6;9) leukaemia is commonly associated with bone marrow basophilia, the cytological characteristics of leukaemic cells are unclear. In the current study, we examined the in vitro effects of several cytokines on growth and differentiation of t(6;9) leukaemic cells. Isolated bone marrow mononuclear cells from four patients with t(6;9) (two MDS and two AML) were cultured for 14 d in the presence or absence of each cytokine. At the end of culture, viable cells were counted, and their histology was examined. Bone marrow cells obtained from 22 patients (10 AML, six AML from MDS, six MDS) lacking t(6;9) were used as controls. Compared with control cultures, significantly higher numbers of blasts appeared in the culture of bone marrow cells from t(6;9)-positive patients in response to stimulation with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) or interleukin 3 (IL-3). Stem cell factor (SCF) had little effect. Neutrophil counts were also significantly increased in the presence of G-CSF or IL-3. SCF and IL-3 were potent in increasing basophil counts from t(6;9)-positive cultures. These findings suggest that bone marrow cells obtained from t(6;9) patients are highly sensitive to growth- and/or differentiation-promoting cytokines. Special attention should be paid to the use of "therapeutic" cytokines in these patients.
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PMID:Effect of cytokines on growth and differentiation of leukaemic cells with translocation t(6;9)(p23;q34). 1184 14

Seventy-seven patients were identified with Rare recurring (excluding 11q23, 21q22, inv(16), and t(15;17)) chromosome abnormalities among 511 patients with treatment-related myelodysplastic syndromes and acute leukemia accepted from centers in the United States, Europe, and Japan. The abnormality subsets included 3q21q26 (17 patients), 11p15 (17 patients), t(9;22)(q34;q11) (10 patients), 12p13 (9 patients), t(8;16)(p11;p13) (9 patients), and an "other" subset, which included t(6;9)(p23;q34) (3 patients), t(10;11)(p13;q13 approximately q21) (3 patients), t(1;17)(p36;q21) (2 patients), t(8;14)(q24;q32) (2 patients), t(11;19)(q13;q13) (2 patients), t(1;3)(p36;q21) (2 patients), and t(3;5)(q21;q31) (1 patient). Increased karyotypic complexity with additional balanced and unbalanced rearrangements was observed in 70% of cases. Among 54 cases with secondary abnormalities, chromosome 5 and/or 7 abnormalities were observed in 59%. The most frequent primary diseases were breast cancer (24 cases), Hodgkin disease (14 cases), non-Hodgkin lymphoma (10 cases), and de novo ALL (5 cases). Thirty-seven patients received alkylating agents plus topoisomerase II inhibitors with or without radiation therapy. The presenting diagnosis was t-AML in 47 cases, t-MDS in 23 cases (10 progressed to t-AML), and t-ALL in seven cases, five of whom had a t(9;22). The median latency time from initiation of original therapy to therapy-related disease diagnosis was quite long (69 months), and the overall median survival from the date of therapy-related disease diagnosis was very short (7 months). The 1-year survival rate was 34 +/- 7%, with no significant differences among subsets. Comparison with previously reported cases showed increased karyotypic complexity and adult presentation of pediatric-associated chromosome abnormalities.
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PMID:Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop. 1192 Dec 74

Chromosomal aberrations have been reported in most malignant hematopoietic disorders such as acute or chronic myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndromes. Eosinophilic leukemia is a rare hematologic malignancy difficult to distinguish from other forms of idiopathic hypereosinophilic syndrome, so that the diagnosis is often made by exclusion, unless cytogenetic abnormalities can be demonstrated in bone marrow cells. We describe a patient with eosinophilic leukemia whose cytogenetic study shows a t(2;5)(p23;q31). Initial data could suggest a clonal eosinophilia, with an hepatosplenomegaly, severe pancytopenia, and a high level of blood and medullar eosinophilia.
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PMID:Eosinophilic leukemia associated with t(2;5)(p23;q31). 1194 46

In this study, we examined a pediatric case of therapy-related myelodysplastic syndrome (tMDS). The symptoms developed 17 months after treatment for acute myeloblastic leukemia (AML, M2 subtype according to the French-American-British [FAB] classification) involving a chromosome abnormality at t(8;21)(q22;q22). Upon diagnosis of tMDS, spectral karyotyping analysis detected a new chromosomal translocation at t(2;8)(p23;p11.2). In addition, fluorescence in situ hybridization analysis suggested a rearrangement in the monocytic leukemia zinc finger (MOZ) gene, located in the 8p11 region of chromosome 8. However, no partner gene on 2p23 could be identified. To our knowledge, this is the first report of tMDS associated with a rearrangement of the MOZ gene. MOZ-linked fusion proteins such as MOZ-CBP (CREB binding protein), MOZ-TIF2 (transcriptional intermediary factor 2), and MOZ-p300 (adenoviral E1A-associated protein) are associated with AML chromosomal abnormalities at t(8;16)(p11;p13), inv(8)(p11q13), and t(8;22)(p11;q13), respectively, and are thought to account for leukemogenesis occurring through the aberrant regulation of histone acetylation. Through a similar mechanism, we believe that MOZ, fused to an unidentified partner gene at 2p23, may have caused an alteration in histone acetylation, resulting in the development of tMDS in this patient.
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PMID:Rearrangement of the MOZ gene in pediatric therapy-related myelodysplastic syndrome with a novel chromosomal translocation t(2;8)(p23;p11). 1261 66

The clinical, hematological, and cytogenetic data from a 4 year-old child with acute myeloid (AML-M1) and basophilia is reported. Interestingly, cytogenetic investigations revealed the presence of the translocation t(6;9) (p23;q34). This abnormality is rare and associated with myelodysplastic syndromes or with subtypes of acute myeloid leukemia (M1, M2, M4, M7), usually with preceding or underlying myelodysplasia. The prognosis is poor, without response to chemotherapy regimen alone. Allogeneic bone marrow transplantation appears likely to be a more appropriate treatment.
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PMID:[Acute myeloblastic leukemia without maturation (AML-M1) with basophilic elements and associated with translocation t(6;9)]. 1280 15

Chromosomal rearrangements involving 3q26 either due to inversion or translocation with various partner chromosomes are a recurrent finding in malignant myeloid disorders. Typically, these chromosome aberrations contribute to ectopic expression of or to the formation of fusion genes involving the EVI1 proto-oncogene. Chromosomal translocations involving the short arm of chromosome 2 (p15-p23) and the distal part of the long arm of chromosome 3 (q26-q27) are a rare but recurrent finding in patients with myeloid malignancies, and are assumed to be part of this spectrum of disorders. Thus far, however, these translocations have been poorly studied. Here, we present 21 new cases with myelodysplasia, acute myeloid leukemia or CML in blast crisis, which upon karyotyping showed the presence of a t(2;3). Furthermore, an extensive literature review disclosed 29 additional cases. Morphological, clinical and cytogenetic assessment revealed the typical hallmarks of 3q26/EVI1 rearrangements, that is, trilineage dysplasia and dysmegakaryopoiesis, poor prognosis and additional monosomy 7. Molecular cytogenetic analysis and PCR in selected samples indicated that in most cases the translocation indeed targets the EVI1 locus. Mapping of the chromosome 2 breakpoints confirmed the initially suspected cytogenetic breakpoint heterogeneity at the 2p arm.
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PMID:Translocation t(2;3)(p15-23;q26-27) in myeloid malignancies: report of 21 new cases, clinical, cytogenetic and molecular genetic features. 1508 64

Polycomb group proteins are implicated in embryogenesis and carcinogenesis through transcriptional regulation of target genes. ASXL1 and ASXL2 genes, encoding Polycomb group protein with ASXN and ASXM domains, are human homologs of Drosophila additional sex combs (asx) gene. Exons 2-13 of the ASXL2 gene are fused to exons 1-14 of the MYST3 gene in a case of therapy-related myelodysplastic syndrome due to t(2;8)(p23.3;p11.2). Here, we identified the ASXL3 gene, a novel human homolog of Drosophila asx, by using bioinformatics. ASXL3 gene, consisting of 12 exons, was located within human genome sequences RP11-562H1 (AC023192.8), RP11-265C19 (AC090989.8), and RP11-470B24 (AC010798.9). Complete coding sequence of human ASXL3 cDNA was determined by assembling EST BE145544, exons 4-11, and 5'-truncated KIAA1713 cDNA (AB051500.2). Partial coding sequence of mouse Asxl3 cDNA was derived from 3'-truncated C230079D11 cDNA (AK082659.1). Human ASXL3 mRNA was expressed in pancreatic islet, testis as well as in neuroblastoma, head and neck tumor. Human ASXL3 protein (2248 aa) with ASXN, ASXM and PHD domains was the third member of the human ASXL family. The region between ASXM and PHD domains was divergent among ASXL family members. Proline-rich domain was located within the divergent region of ASXL3, but not within that of ASXL1 and ASXL2. ASXL3-DTNA locus at chromosome 18q12.1 and ASXL2-DTNB locus at 2p23.3 were paralogous regions within the human genome. ASXL3 was a predicted cancer-associated gene, just like ASXL1 and ASXL2. This is the first report on identification and characterization of the ASXL3 gene.
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PMID:Identification and characterization of ASXL3 gene in silico. 1513 7

We report on a patient fulfilling the diagnostic criteria of unclassifiable myelodysplastic/myeloproliferative diseases with prominent erythropoietic hyperplasia/dysplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24). The patient presented with B-symptoms, erythroblastemia, thrombopenia, marked eosinophilia, presence of myeloid precursors in the peripheral blood, and decreased erythropoietin level. Nodular peritrabecular polymorphous blasts, dysplastic megakaryocytes, and a diffuse argyrophilic fibrosis were detected in the trephine bone marrow biopsy. Immunohistochemically, the blasts stained positively for glycophorin C and hemoglobin A; the proliferation fraction was nearly 90% in the Ki-67 stain. Expression of the phosphorylated Janus kinase 2 was detected in almost all megakaryocytes and in isolated erythroblast islets, suggesting a probable activation of Janus kinase 2, the jak-2 gene being mapped on 9p24. Ten months after initial diagnosis, the disease progressed to frank acute erythroid leukemia. We report for the first time a myelodysplastic/myeloproliferative disease (erythroid preleukemia) accompanied by the specific chromosomal aberration t(8;9)(p23;p24), distinct histopathology, and clinical and laboratory symptoms, and progress to acute erythroid leukemia.
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PMID:Myelodysplastic/myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): first description of a case. 1656 30

Acute myelogenous leukemia (AML) with chromosomal translocation (6;9)(p23;q34) is a rare disease with poor prognosis and distinct clinical and morphologic features. t(6;9) results in a chimeric fusion gene between DEK (6p23) and CAN/NUP214 (9q34). FLT3-ITD mutation is one of the most frequent mutations in AML and correlates with poor clinical outcome. Prevalence of FLT3-ITD is as high as 70% among patients with t(6;9) AML, and patients with t(6;9) AML and FLT3-ITD mutations usually have higher white blood cell counts, higher bone marrow blasts, and significantly lower rates of complete remission. t(6;9) is most commonly associated with AML-FAB-M2 and is considered by some researchers to be a separate disease entity because of its distinct clinical and morphologic features and poor prognostic implication. Distinct morphologic features of this entity include marrow basophilia and myelodysplasia, and immunophenotypically, the blast cells are positive for CD9, CD13, CD33, and HLA-DR; are usually positive for CD45 and CD38; and may be positive for CD15, CD34, and terminal deoxynucleotidyl transferase.
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PMID:Acute myelogenous leukemia with t(6;9)(p23;q34) and marrow basophilia: an overview. 1897 25

Myeloid leukemia in this series corresponds to the myeloid neoplasms of the 4th WHO classification of pathology and genetics of tumor of haematopoietic and lymphoid tissue. The myeloid neoplasms are composed of six categories, which are 1) myeloproliferative neoplasms (MPN), a new category of 2) myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1, 3) myelodysplastic syndrome (MDS)/MPN, 4) MDS, 5) acute myeloid leukemia (AML) and related precursor neoplasms, and 6) acute leukemias of ambiguous lineage. In MPNs without chronic myelogenous leukemia, the genetic marker of JAK2 V617F is added to the diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. MDS has the new subtype of refractory cytopenia with unilineage dysplasia composed of refractory anemia, refractory neutropenia and refractory thrombocytopenia. AML with t(9; 11) (p22;q23); MLLT3-MLL, AML with t(6;9) (p23; q34); DEK-NUP214, AML with inv(3) (q21q26.2) or t(3; 3) (q21 ; q26.2); RPN1-EVI1 and AML (megakaryoblastic) with t(1; 22) (p13; q13); RBM15-MKL1 are added to the subtype of AML with recurrent genetic abnormalities, and AML with gene mutations of NPM1 and CEBPA are also added as provisional entities of it. The myeloid neoplasms of the 4th WHO classification are comprehensive and seem to be dynamic by incorporating the results of leukemia researches.
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PMID:[Classification of myeloid leukemias]. 1986 Jan 79


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