Apparently Unrelated Clones Shown by Spectral Karyotyping to Represent Clonal Evolution of Cryptic t(10;11)(p13;q23) in a Patient with Acute Monoblastic Leukemia

Stark, Batia; Jeison, Marta; Gobuzov, Rima; Finkelshtein, Sharon; Ash, Susan; Avrahami, Gali; Cohen, Ian J.; Stein, Jerry; Yaniv, Isaac; Zaizov, Rina; Bar‐Am, Irit

doi:10.1016/s0165-4608(00)00211-9

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…25 Although these complex rearrangements may be readily visible at the cytogenetic level, in some instances the chromosomal defect may be subtle or even cryptic. 13,25,33 Using multicolor FISH with locus-specific probes, we have investigated the chromosomal nature of two MLL-MLLT10-positive chromosome 10;11 rearrangements. In the first patient, at least four breakpoints must have occurred in order to explain the observed FISH results.…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

et al. 2002

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MLLT10(previously called AF10) is a moderately common MLL fusion partner predominantly occurring in acute monoblastic leukemia (AML-M5). 10;11 rearrangements require at least three breaks in order to generate an in-frame MLL-MLLT10 fusion as a result of the opposite orientations of both genes on the respective chromosome arms. In this study, we describe a detailed molecular cytogenetic analysis of MLL-MLLT10 positive 10;11 rearrangements in two patients. We observed an as yet unreported chromosomal mechanism with at least four breakpoints, leading to MLL-MLLT10 gene fusion in a 24-yearold male. An inversion of 11q13-q23 with a breakpoint in the MLL gene was followed by an additional break 3′ of MLL prior to insertion of the 11q segment into MLLT10. In a second patient, a 37-year-old male with AML-M5b, molecular cytogenetic analysis of an apparent 10;11 reciprocal translocation showed an intrachromosomal inversion of 3′MLLT10 followed by a reciprocal translocation between 10p12 and 11q23. Review of the literature showed that all cases were the result of an inversion of either 10p or 11q followed by translocation 10p;11q or insertion of the inverted segment into MLLT10 or MLL.

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Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

et al. 2002

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“…Slides were hybridized with the spectral karyotype (SKY) probe mixture obtained from Applied Spectral Imaging (Migdal Ha'emek, Israel) as previously described (Stark et al , 2000). The SKY slides were analysed with the skyview software on the SD300 Spectral Imaging system (Applied Spectral Imaging).…”

Section: Spectral Karyotype Analysismentioning

confidence: 99%

Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukaemia: report from a referral centre in Israel

Stark¹,

Jeison²,

Gabay³

et al. 2004

Br J Haematol

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Summary The incidence of cytogenetic abnormalities in childhood de novo acute myeloid leukaemia (AML) and its prognostic significance was assessed in an Israeli paediatric referral centre. Cytogenetic analysis was successful in 86 of 97 children (<20 years of age) diagnosed between 1988 and 2002 with de novo AML. Fluorescence in situ hybridization analysis detected new information in 11 of them, leading to reassignment in cytogenetic group classification. The incidence of the various cytogenetic subgroups was as follows: normal – 9%; t(11q23) – 22%; t(8;21) – 13%; t(15;17) – 8%; inv(16) – 3·4%; abn(3q) – 4·6%; 7/7q‐(sole or main) – 5·8%; del(9q)(sole) and +21(sole) – 4·6% each; t(8;16) – 2·3%; t(6;9), t(1;22), +8(sole) – 1·1% each; and miscellaneous – 18%. The overall survival (OS) and event‐free survival (EFS) (4 years) for 94 patients treated with the modified Berlin‐Frankfürt‐Münster (BFM) AML protocols (non‐irradiated) were 59·9% (SE = 5%) and 55·7% (SE = 5%), respectively, and for the favourable t(8;21), t(15;17) and inv(16), OS was 60% (SE = 15%), 83% (SE = 15%) and 100% respectively. For the normal group it was 62% (SE = 17%), miscellaneous 64% (SE = 12%), t(11q23) 44·6% (SE = 11%) and of the −7/7q‐, del(9q)(sole) or t(6;9), none had survived at 4 years. The incidence of cytogenetic subgroups in the Israeli childhood AML population and their outcome were similar to other recently reported paediatric series. Cytogenetic abnormalities still carry clinical relevance for treatment stratification in the context of modern chemotherapy.

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“…that the clones are in fact genetically related, for example via a cytogenetically cryptic aberration such as t(12; 21)(p13;q22) in ALL. Indeed, 1 such example has been reported in the literature, a translocation detected by multicolor FISH in an AML with seemingly unrelated clones [Stark et al, 2000]. It is likely that novel methods such as massively parallel sequencing of whole leukemic genomes will show that the vast majority of cytogenetically polyclonal acute leukemias in fact harbor genetically related clones.…”

Section: Genomic Heterogeneity On the Cytogenetic Level: Polyclonal Amentioning

confidence: 99%

Genomic Heterogeneity in Acute Leukemia

Paulsson¹

2013

Cytogenet Genome Res

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Acquired genetic aberrations are the underlying cause of leukemogenesis in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The karyotypes of AML and ALL cases are generally quite simple as seen by chromosome banding analysis, with few genetic changes and a limited number of subclones. However, investigations using fluorescence in situ hybridization, loss of heterozygosity analysis, single-nucleotide polymorphism arrays, and, most recently, massively parallel sequencing have challenged this view. In particular, comparison of diagnostic and relapse samples, modeling in transgenic mice, and whole-exome and whole-genome sequencing have indicated that widespread genomic heterogeneity, which is masked by a dominant clone, may be present in AML and ALL. In the present review, our current knowledge of genomic heterogeneity in acute leukemia is summarized.

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Apparently Unrelated Clones Shown by Spectral Karyotyping to Represent Clonal Evolution of Cryptic t(10;11)(p13;q23) in a Patient with Acute Monoblastic Leukemia

Cited by 12 publications

References 26 publications

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia

Classical and molecular cytogenetic abnormalities and outcome of childhood acute myeloid leukaemia: report from a referral centre in Israel

Genomic Heterogeneity in Acute Leukemia

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