High hyperdiploid acute lymphoblastic leukemia in adults shows clonal heterogeneity and chromosomal instability at diagnosis and during the course of the disease

Abstract

Dear Editor, High hyperdiploidy with 51–67 chromosomes (HeH) constitutes a large cytogenetic subset of B cell precursor childhood acute lymphoblastic leukemia (ALL) [1]. It is much less common in adult B cell precursor ALL where it was reported in nearly 10% of patients for whom outcome was improved compared to the other cytogenetic groups, but not as favorable as in children [2, 3]. It is rarely found in T cell or mature B cell ALL. Automated four-color interphase fluorescence in situ hybridization (I-FISH) previously revealed a high level of clonal aneuploidy heterogeneity in HeH ALL at presentation [4]. Numerical chromosome instability (CIN) was supposed to be at the origin of this heterogeneity. To assess the presence of clonal heterogeneity and numerical CIN in adult HeH ALL at diagnosis and during disease course, we focused on a series of ten ALL patients selected according to the presence of HeH by conventional cytogenetics, age, and availability of material for four-color I-FISH investigation using probes specific to chromosomes 4, 6, 10, and 17 (Supplement 1). Probes were chosen based on the frequent gain of these chromosomes in HeH ALL and its prognostic significance [5]. Patients were referred between 1995 and 2009 from the university hospitals of Basel, Zurich, Bern, Lausanne and cantonal/regional hospitals of St-Gallen, Aarau, Mendrisio, Bellinzona, and Genolier Clinic. Two patients were enrolled in the SAKK ALL 33-86/90 [6] and GRAALL 2005 clinical trials, respectively. Ethical approval for this project was obtained in accordance with the guidelines of the local Ethical Review Board. Thirty-four samples were analyzed (presentation, 7; hematologic remission, 19; relapse, 8); status of heterogeneity and CIN level were determined (Table 1, Supplement 2). Significant aneuploidies were identified based on cutoff values defined according to the Poisson distribution, and combinations of aneuploidies were considered relevant when at least one aneuploidy was determined to be significant. Average CIN was determined for all four chromosomes together and then for each selected chromosome. Approaches used and cutoff levels were reported in detail previously [4, 7]. Electronic supplementary material The online version of this article (doi:10.1007/s00277-011-1317-x) contains supplementary material, which is available to authorized users.