1/21. A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer cytogenetics Group (UKCCG)Partial deletion of the long arm of chromosome 5, del(5q), is the cytogenetic hallmark of the 5q-syndrome, a distinct subtype of myelodysplastic syndrome-refractory anemia (MDS-RA). Deletions of 5q also occur in the full spectrum of other de novo and therapy-related MDS and acute myeloid leukemia (AML) types, most often in association with other chromosome abnormalities. However, the loss of genetic material from 5q is believed to be of primary importance in the pathogenesis of all del(5q) disorders. In the present study, we performed fluorescence in situ hybridization (FISH) studies using a chromosome 5-specific whole chromosome painting probe and a 5q subtelomeric probe to determine the incidence of cryptic translocations. We studied archival fixed chromosome suspensions from 36 patients with myeloid disorders (predominantly MDS and AML) and del(5q) as the sole abnormality. In 3 AML patients studied, this identified a translocation of 5q subtelomeric sequences from the del(5q) to the short arm of an apparently normal chromosome 11. FISH with chromosome 11-specific subtelomeric probes confirmed the presence of 11p on the shortened 5q. Further FISH mapping confirmed that the 5q and 11p translocation breakpoints were the same in all 3 cases, between the nucleophosmin (NPM1) and fms-related tyrosine kinase 4 (FLT4) genes on 5q35 and the Harvey ras-1-related gene complex (HRC) and the radixin pseudogene (RDPX1) on 11p15.5. Importantly, all 3 patients with the cryptic t(5;11) were children: a total of 3 of 4 AML children studied. Two were classified as AML-M2 and the third was classified as M4. All 3 responded poorly to treatment and had short survival times, ranging from 10 to 18 months. Although del(5q) is rare in childhood AML, this study indicates that, within this subgroup, the incidence of cryptic t(5;11) may be high. It is significant that none of the 24 MDS patients studied, including 11 confirmed as having 5q-syndrome, had the translocation. Therefore, this appears to be a new nonrandom chromosomal translocation, specifically associated with childhood AML with a differentiated blast cell phenotype and the presence of a del(5q).- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
2/21. Identification of breakpoint cluster regions at 1p36.3 and 3q21 in hematologic malignancies with t(1;3)(p36;q21).The reciprocal translocation t(1;3)(p36;q21) is associated with myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) characterized by trilineage dysplasia, in particular dysmegakaryocytopoiesis, and a poor prognosis. As yet no molecular genetic analyses of the t(1;3) have been reported. In four patients with t(1;3), all of whom had AML-M4, which evolved from MDS, the breakpoints at 3q21 clustered within a 60-kb region centromeric to the breakpoint of the inv(3)(q21q26), whereas the breakpoints at 1p36 clustered within a 90-kb region at 1p36.3. The presence of novel clusters in both the 3q21 and 1p36 breakpoints (BCRs) suggests a common, underlying molecular mechanism for the development of t(1;3)-positive MDS/AML. The Ribophorin I (RPN1) gene close to the BCR at 3q21 was highly expressed without gross structural changes, whereas the GR6 gene located within the BCR at 3q21 was not expressed. No other highly expressed genes were isolated in a 150-kb region at 3q21. Thus, it is likely that a gene at 1p36.3 is activated by the translocation of the 3q21 region or a gene important for transformation lies on 3q21, outside the 150-kb region. Further characterization of the BCRs at 1p36.3 and 3q21 should provide important insights into the molecular genetic mechanisms involved in the genesis of t(1;3)-positive MDS/AML. genes chromosomes Cancer 27:229-238, 2000.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
3/21. Generation of the NUP98-HOXD13 fusion transcript by a rare translocation, t(2;11)(q31;p15), in a case of infant leukaemia.We report a case of de novo acute myelomonocytic leukaemia with the t(2;11)(q31;p15) translocation in a Japanese female infant. The NUP98-HOXD13 fusion transcript generated by the translocation was detected in the patient's bone marrow cells by reverse transcription-polymerase chain reaction (RT-PCR). Additionally, ectopic expression of the normal allele of the HOXD13 gene was observed in this patient, suggesting that it might be associated with leukaemogenic development. This case is the third report of t(2;11) leukaemia with NUP98-HOXD13 and the first report showing that NUP98 rearrangements are associated with infant leukaemia, as well as therapy-related acute myelogenous leukaemia or myelodysplastic syndrome.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
4/21. Amplification of ERBB2, RARA, and TOP2A genes in a myelodysplastic syndrome transforming to acute myeloid leukemia.A patient is described with myelodysplastic syndrome (MDS) progressing to acute myeloid leukemia (AML) FAB M4. cytogenetic analysis revealed an unusual rearrangement between chromosomes 9 and 17, leading to a dicentric chromosome with an insertion of material of unknown origin between both chromosomes. By fluorescence in situ hybridization (FISH), the insertion was shown to be an amplification of part of 17q, involving ERBB2, RARA, and TOP2A genes. The median copy number of ERBB2, RARA, and TOP2A genes in the tumor cells was six (range: 4--10). Only one copy of the MPO gene at 17q21.3 was detected, suggesting a deletion of the telomeric part of 17q. To our knowledge, this is the first report of a 17q amplification in AML.- - - - - - - - - - ranking = 5keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
5/21. New acute myeloid leukemia-derived cell line: MUTZ-8 with 5q-.The advent of continuous human leukemia-lymphoma cell lines as a rich resource of abundant, accessible and manipulable living cells has contributed significantly to a better understanding of the pathophysiology of hematopoietic tumors. We describe the establishment of the new continuous leukemia cell line MUTZ-8 from a patient with acute myeloid leukemia (AML): MUTZ-8 was derived from the peripheral blood of a 63-year-old woman with AML M4 (25 years after onset of myelodysplastic syndromes, MDS). dna fingerprinting confirmed authenticity and derivation of the cell line. The immunoprofiling as determined by flow cytometry showed that MUTZ-8 is positive mainly for myeloid but also some monocytic and megakaryocytic markers, whereas it is negative for T cell, B cell and erythroid markers. The cell line is constitutively cytokine-dependent, proliferation requiring externally added cytokines. The cytokine response profiles showed a two- to 10-fold growth stimulation of the cells by various cytokines, whereas other cytokines led to growth inhibition. cytogenetic analysis confirmed the common clonal derivation of the cell line and the malignant clone predominating at the times of sampling. MUTZ-8 displays a deletion of the 5q31 AML/MDS region effected by a non-reciprocal translocation, t(5;11)(q21;q10). The scientific utility of MUTZ-8 lies (1) in its cluster of pathognomonic cytogenetic alterations including a 5q31 breakpoint and (2) in its absolute cytokine dependency and proliferative response to various cytokines.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
6/21. Translocation (8;12)(q13;p13) during disease progression in acute myelomonocytic leukemia with t(11;19)(q23;p13.1).We report here the first case of acute myelomonocytic leukemia (AMMoL) with both t(8;12)(q13;p13) and t(11;19)(q23;p13.1). A 75-year-old woman was initially diagnosed as having AMMoL with t(11;19) (q23;p13) as a sole abnormality. At the second relapse, G-banding analysis of the bone marrow cells showed 46,XX,t(11;19)(q23;p13)/46,XX,t(8;12)(q13;p13),t(11;19)(q23;p13). fluorescence in situ hybridization analysis with chromosome-specific painting probes confirmed both the der(8)t(8;12) and the der(12)t(8;12). reverse transcription-polymerase chain reaction analysis detected the MLL/ELL fusion transcript, indicating that the breakpoint on chromosome 19 was 19p13.1. Leukemic cells at the second relapse were positive for CD2, CD13, CD33, and CD34 but negative for CD14 and HLA-DR. The patient died within 2 months after a subclone with t(8;12)(q13;p13) had appeared. In the literature, t(8;12)(q12;p13) has been observed in two cases of myelodysplastic syndrome and one case of acute myeloblastic leukemia. Our results indicated that t(8;12)(q13;p13) may be one of the recurrent aberrations in myeloid malignancies, although molecular heterogeneity of the breakpoints might exist. Furthermore, it is suggested that t(8;12)(q13;p13) may play an important role in the progression of the disease and lead to the poor prognosis.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
7/21. Breakpoints at 1p36.3 in three MDS/AML(M4) patients with t(1;3)(p36;q21) occur in the first intron and in the 5' region of MEL1.The recurrent translocation t(1;3)(p36;q21) is associated with myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and a poor prognosis. Recently, the two genes involved in this translocation have been identified: the MEL1 gene at 1p36.3, and the RPN1 gene at 3q21. The breakpoint in RPN1 is centromeric to the breakpoint cluster region of the inv(3) abnormality. Because the MEL1 transcript is detected only in leukemic cells with t(1;3)(p36;q21), ectopic expression of MEL1 driven by RPN1 at 3q21 is thought to contribute to the pathogenesis of t(1;3)(p36;q21) leukemia. However, the precise breakpoint in the patients has not yet been identified. With fluorescence in situ hybridization analysis by use of BAC/PAC probes, we identified the breakpoint at 1p36.3 in three MDS/AML patients with t(1;3)(p36;q21): within the first intron of the MEL1 gene (one patient) or within a 29-kb region located in the 5' region of MEL1 (two other patients). We detected several sizes of MEL1 transcript in two patients including the first patient, although we have not yet clarified whether MEL1 transcripts were different among the patients and whether a truncated MEL1 transcript was expressed in the first patient. This patient showed an unusual clinical profile, repeating progression to overt leukemia and conversion to MDS three times during the 29-month survival period, which might be related to a different molecular mechanism in this patient.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
8/21. Disseminated cutaneous granulomatous eruption occurring in the setting of myelodysplasia.A 66-year-old woman with a myelodysplastic syndrome developed a widespread, pruritic, nodular eruption. A skin-biopsy specimen showed a granulomatous infiltrate, with no evidence of clonality; a bone-marrow biopsy showed possible transition to acute myeloid leukemia. This presentation is consistent with two prior reports of granulomatous eruptions occurring in the setting of myelodysplasia.- - - - - - - - - - ranking = 1keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
9/21. Blastic natural killer-cell lymphoma of the skin associated with myelodysplastic syndrome or myelogenous leukaemia: a coincidence or more?We report three patients with blastic natural killer (NK)-cell lymphoma of the skin associated with myelodysplastic syndrome (MDS) (two patients) or subacute myelomonocytic leukaemia (one patient). In two patients MDS was diagnosed before skin lesions; the patient with leukaemia initially presented with skin lesions. Our patients had several clinical features in common, namely multiple skin lesions with a bruise-like appearance, involvement of the oral mucosa, and good general status at presentation but very rapid deterioration in the course of the disease. All patients died of disease 4-14 months after the diagnosis. Histopathologically, there were cutaneous infiltrates of slightly pleomorphic medium-sized cells expressing CD4, CD56, terminal deoxynucleotidyl transferase (focally) and being negative for surface CD3, cytotoxic molecules, B-cell-associated markers and myelomonocytic markers. Erythrocyte extravasation was seen in all patients. T-cell receptor genes were in germline configuration. MDS was classified as refractory cytopenia with multilineage dysplasia and ring sideroblasts and refractory anaemia with transition to refractory anaemia with excess of blasts. We reviewed similar cases reported in the literature showing coexistence of blastic NK-cell lymphoma/leukaemia and MDS or myelogenous leukaemia. We conclude that given an overall limited number of reported cases of blastic NK-cell lymphoma/leukaemia, its association with various myelodysplastic/myeloproliferative disorders seen in a subset of patients ( approximately 15-20%) is more than coincidental and may indicate their common origin.- - - - - - - - - - ranking = 2.6146179634743keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
10/21. Therapy-related myelodysplastic syndrome in children with medulloblastoma following MOPP chemotherapy.Between 1978 and 1988, 20 children with medulloblastoma (MB) of the brain were treated postoperatively with MOPP (nitrogen mustard, vincristine, prednisone, and procarbazine). All but one received post-operative radiation prior to MOPP. Eight of 20 patients remained in continuous complete remission from MB, two of whom eventually developed myelodysplastic syndrome (MDS). Following resection of MB at age 12 months, one patient was treated with 24 courses of MOPP over 2 years without radiation therapy. She developed pancytopenia, and MDS was diagnosed 19 months after the completion of MOPP. Analysis of unstimulated bone marrow (BM) chromosomes showed structural abnormalities involving chromosomes 7, 10, 17, and 21. Eight months later, MDS evolved into acute myeloid leukemia. The second patient was diagnosed with MB at age 7 years and received postoperative craniospinal radiation followed by 12 courses of MOPP over one year. Five months after completion of MOPP, she developed MDS with monosomy 7 on chromosome analysis of bone marrow cells. Therapy-related MDS may be a complication of MOPP chemotherapy for MB in young children.- - - - - - - - - - ranking = 5keywords = myelodysplastic syndrome, myelodysplastic (Clic here for more details about this article) |
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