Probes for hidden hyperdiploidy in acute lymphoblastic leukaemia

Moorman, Anthony V.; Clark, Roslyn; Farrell, Dianna M.; Hawkins, Jacqueline M.; Martineau, Mary; Secker-Walker, LM

doi:10.1002/(sici)1098-2264(199605)16:1<40::aid-gcc6>3.0.co;2-3

Cited by 41 publications

(22 citation statements)

References 15 publications

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“…High-hyperdiploidy in ALL has a distinct nonrandom pattern, with gain of chromosomes X, 4, 6, 14 and 21 being most frequently observed. 6 The high-hyperdiploid pattern in our patients showed similar patterns of chromosome gain. High-hyperdiploid ALL blasts are known to have a marked propensity for apoptosis in vitro, which has been linked to the relatively good in vivo response to chemotherapy.…”

Section: Discussionsupporting

confidence: 70%

High-hyperdiploidy in Philadelphia positive adult acute lymphoblastic leukaemia: case-series and review of literature

Tauro¹,

McMullan

Griffiths

et al. 2003

Bone Marrow Transplant

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Summary:Patients with Philadelphia positive (Ph + ) adult acute lymphoblastic leukaemia (ALL) have a poor prognosis. Stem cell transplantation (SCT) is increasingly being recognised as the treatment of choice in eligible patients with Ph + ALL, but disease-relapse remains a problem in a proportion of patients prior to and after SCT. Genetic abnormalities in addition to the Ph chromosome may influence the biology and clinical course of ALL, but there are not many studies on the potential genetic heterogeneity of adult Ph + ALL and clinical outcomes. Here, we report on five patients with ALL who were double Ph + and also had a high-hyperdiploid karyotype (Ph + / hyperdiploid) at diagnosis. In contrast to the presence of the Ph + chromosome, high-hyperdiploidy (450 chromosomes) as the sole karyotypic abnormality in ALL is associated with a favourable clinical outcome. In our series, four patients with a Ph + /hyperdiploid karyotype achieved a cytogenetic remission after induction chemotherapy and proceeded to stem cell transplantation (SCT). The fifth had five subclones including Ph + / hyperdiploid, as well as those that were only Ph + ; the latter emerged as the dominant clone after induction therapy and the patient died of disease-relapse. Of the patients who underwent SCT, only one relapsed, but achieved a durable remission with donor lymphocyte infusions. Thus, it is conceivable that the presence of high-hyperdiploidy as an additional karyotypic abnormality may confer a better prognosis to Ph + ALL, presumably by altering the kinetics of Ph + neoplastic cells. We have discussed these results in the context of recent studies on the significance of high-hyperdiploidy in Ph + adult ALL.

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Section: Discussionsupporting

confidence: 70%

High-hyperdiploidy in Philadelphia positive adult acute lymphoblastic leukaemia: case-series and review of literature

Tauro¹,

McMullan

Griffiths

et al. 2003

Bone Marrow Transplant

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“…5,30 In addition, particular karyotype patterns may have specific prognostic implications. [2][3][4]6 Our evaluation of the CGH technique in hyperdiploid ALL confirms that CGH is a valuable adjunct for the unequivocal assessment of such quantitative changes.…”

Section: Discussionmentioning

confidence: 99%

“…However, a reliable detection of only the most common numerical deviations in such hyperdiploid cases with conventional FISH requires at least four to six probes in several hybridization steps. 5 Thus, compared to conventional FISH screening, CGH clearly provides a representative overview of quantitative deviations which, in addition, is obtainable in only one single hybridization experiment. Considering these facts, CGH is also a costefficient technique.…”

Section: Discussionmentioning

confidence: 99%

“…As expected, most of the chromosomal changes involved were gains of complete chromosomes. Structural Table 2 Summary +X,+4,+6,+9,+10,+14,+17,+18, 46,XY,der(7) [3] +21,+21 56,XY,+X,+4,+6,der(7),+9,+10,+14,+17,+18,+21,+21 [5] 9 54,XY,+X,+4,+8,+9,+9,+14,+21,+22 [10] +X,+4,+8,+9,+9,+14,+17,+19, 4 × 21 (84%) +21,(+21),+22 10 55-58,XY,+X,+4,+4,+5,+6,+8,+10,+14,+17,+18,+21,+21 +X,+4,+4,+5,+6,+8,+10,+14,+17,…”

Section: Classical Banding Analysismentioning

confidence: 99%

“…[1][2][3][4][5][6][7] The unequivocal determination of the karyotype composition could be of great importance and might eventually be used for the stratification of clinical therapy. [2][3][4]6 Hyperdiploidy with more than 50 chromosomes or a DNA content Ͼ1.16 is one of the strongest predictors for an extremely low risk of failing chemotherapy, regardless of the white blood cell count (WBC).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparative genomic hybridization as part of a new diagnostic strategy in childhood hyperdiploid acute lymphoblastic leukemia

et al. 1998

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The detailed definition of karyotype changes associated with hyperdiploid acute lymphoblastic leukemia (ALL) is a precondition for their exploitation in minimal residual disease studies with fluorescence in situ hybridization analysis (FISH (FISH) showed that all stem lines had been correctly defined by CGH. In eight cases, however, cytogenetic analyses revealed structural abnormalities that were undetectable by CGH. The other discrepancies were mainly due to a cytogenetic misinterpretation of similar sized and shaped chromosomes. Based on these findings we present a new diagnostic strategy for childhood ALL that includes flow cytometry and classical cytogenetics as well as CGH for the analysis of aneuploid cases and FISH to resolve the unavoidable discrepancies.

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