Morphology, cytogenetics, and survival in myelodysplasia with del(20q) or ider(20q): a multicenter study.
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in Annals of Hematology (2012), 91(2), 203-13
Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific ... [more ▼]
Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific morphological pattern nor clear prognostic significance. The aim of this retrospective multicentric study is to compare the peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n = 13) and del(20q) (n = 21) and controls (n = 47) in order to investigate whether the ider(20q) harbors specific morphological features. The secondary objective is to compare the outcome of patients from both groups. This study performed on the largest cohort of MDS patients with ider(20q) is the first that identifies specific morphological features (hypogranulated and vacuolized neutrophils and neutrophil erythrophagocytosis) allowing the identification of this cytogenetic abnormality with high sensitivity (70%) and specificity (85.7%). Suspected ider(20q) by morphology should therefore support targeted FISH tests in case of non informative karyotype. This combined approach will allow a better estimation of the prevalence of this underdiagnozed entity. The overall survival and progression-free survival did not statistically differ in both groups. However, hypogranulated and vacuolized neutrophils were significantly associated with survival. [less ▲]Detailed reference viewed: 23 (4 ULg)
PRDM16 (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
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in British Journal of Haematology (2012), 156(1), 76-88
The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations ... [more ▼]
The PRDM16 (1p36) gene is rearranged in acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21), sharing characteristics with AML and MDS with MECOM (3q26.2) translocations. We used fluorescence in situ hybridization to study 39 haematological malignancies with translocations involving PRDM16 to assess the precise breakpoint on 1p36 and the identity of the partner locus. Reverse-transcription polymerase chain reaction (PCR) was performed in selected cases in order to confirm the partner locus. PRDM16 expression studies were performed on bone marrow samples of patients, normal controls and CD34(+) cells using TaqMan real-time quantitative PCR. PRDM16 was rearranged with the RPN1 (3q21) locus in 30 cases and with other loci in nine cases. The diagnosis was AML or MDS in most cases, except for two cases of lymphoid proliferation. We identified novel translocation partners of PRDM16, including the transcription factors ETV6 and IKZF1. Translocations involving PRDM16 lead to its overexpression irrespective of the consequence of the rearrangement (fusion gene or promoter swap). Survival data suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis despite a simple karyotype and a median age of 65 years. There seems to be an over-representation of late-onset therapy-related myeloid malignancies. [less ▲]Detailed reference viewed: 52 (5 ULg)
Refinement of 1p36 alterations not involving PRDM16 in myeloid and lymphoid malignancies.
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in PLoS ONE (2011), 6(10), 26311
Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups ... [more ▼]
Fluorescence in situ hybridization was performed to characterize 81 cases of myeloid and lymphoid malignancies with cytogenetic 1p36 alterations not affecting the PRDM16 locus. In total, three subgroups were identified: balanced translocations (N = 27) and telomeric rearrangements (N = 15), both mainly observed in myeloid disorders; and unbalanced non-telomeric rearrangements (N = 39), mainly observed in lymphoid proliferations and frequently associated with a highly complex karyotype. The 1p36 rearrangement was isolated in 12 cases, mainly myeloid disorders. The breakpoints on 1p36 were more widely distributed than previously reported, but with identifiable rare breakpoint cluster regions, such as the TP73 locus. We also found novel partner loci on 1p36 for the known multi-partner genes HMGA2 and RUNX1. We precised the common terminal 1p36 deletion, which has been suggested to have an adverse prognosis, in B-cell lymphomas [follicular lymphomas and diffuse large B-cell lymphomas with t(14;18)(q32;q21) as well as follicular lymphomas without t(14;18)]. Intrachromosomal telomeric repetitive sequences were detected in at least half the cases of telomeric rearrangements. It is unclear how the latter rearrangements occurred and whether they represent oncogenic events or result from chromosomal instability during oncogenesis. [less ▲]Detailed reference viewed: 32 (0 ULg)