Prognostic significance of additional chromosome abnormalities in adult patients with Philadelphia chromosome positive acute lymphoblastic leukaemia

Abstract

The clinical and biological significance of additional chromosome aberrations was investigated in a large series of 66 adult patients with Philadelphia (Ph) chromosome positive acute lymphoblastic leukaemia (ALL). Additional chromosome changes were observed in 71% of the cases. 9p abnormalities were identified in 26%, and monosomy 7 as well as hyperdiploid karyotypes 50 were both found in 17% of cases. 9p anomalies were characterized by a low complete remission (CR) rate (58%) and an extremely short median remission duration (MRD: 100 d). In patients with monosomy 7, the poor treatment outcome was confirmed (CR rate 55%: MRD 113 d). In contrast, all patients with hyperdiploid karyotypes 50 achieved CR, and the overall survival was superior to all other Ph-positive ALL patients except those without additional chromosome aberrations. Exclusive rearrangement of the minor breakpoint cluster region of the BCR gene and lack of coexpression of myeloid-associated antigens in cases with 9p anomalies as well as a high frequency of rearrangements of the major breakpoint cluster region of the BCR gene in patients with monosomy 7 (89%) further substantiated that additional chromosome aberrations may characterize distinct subgroups of Ph-positive ALL. Moreover, the necessity of the complementing use of chromosome banding analyses, polymerase chain reaction (PCR) assays, and fluorescence in situ hybridizations in the accurate identification of Ph-positive patients has become evident due to variant Ph translocations in 3%, and negative PCR assays in 4% of the cases.

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

“…Even in this patient, however, Ph + /hyperdiploid clones were undetectable following induction chemotherapy, and disease relapse appeared to originate from subclones that were Ph + , but not hyperdiploid. These results are similar to those reported by Rieder et al 9 , who detected high hyperdiploidy in up to 17% of adults with Ph + ALL. In their series, patients with the Ph + /hyperdiploid karyotype achieved complete remission more readily than patients who did not have an additional hyperdiploid karyotype, although the duration of remission and overall survival was similar in the two groups.…”

“…Data from Thomas et al 8 have also suggested an improved outlook for Ph + ALL patients with the hyperdiploid karyotype compared to those with other karyotypic abnormalities, although the differences in survival did not approach significance. Both these studies 8,9 have indicated the genetic heterogeneity of Ph + ALL in adults that could potentially translate into variable outcomes.…”

High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

“…As far as concerns t-HeH patients with t(9;22), it has been suggested that they either have a more favorable survival and/or treatment response compared with t(9;22)-positive near-diploid ALL 20,21 or the same dismal outcome as all other patients with this translocation. 22,23 The fact that all six t-HeH with t(9;22) in our Nordic cohort achieved complete remission and all but one remain alive would rather agree with the former view ( Table 2; Online Supplementary Table S1). Obviously, larger series are needed to address this clinically important issue, and this is something that will require international collaboration due to the rarity of t-HeH in pediatric patients.…”

Different patterns of homozygous p16INK4A and p15INK4B deletions in childhood acute lymphoblastic leukemias containing distinct E2A translocations

“…40 Similarly, although no molecular data on p16/p15 gene status were reported, 9p deletions were present in 17/66 (26%) adults with Philadelphia chromosomepositive ALL. 41 At this point in time, almost all of the translocations that are observed in Ͼ1% of ALLs and AMLs have been cloned, the involved genes have been identified, and their biochemical functions are under intensive study. 3 To date, p16 and p15 are the only TSGs identified that are inactivated in a significant percentage of leukemias.…”