Clonal heterogeneity and chromosomal instability at disease presentation in high hyperdiploid acute lymphoblastic leukemia

Sequential and hierarchical chromosomal changes and chromosome instability are distinct features of high hyperdiploid pediatric acute lymphoblastic leukemia

“…According to the first approach, a hallmark of it was that the dominant clones made up approximately only one half and one third of all the leukemias in the HeL and HeH subgroups, respectively. These data support an iFISH study of four chromosomes in a few B‐pALL patients that were not genetically subtyped, but are in contrast to the largest available CCA database revealing only one clone in 84% of ALL cases . The discrepancy between CCA and iFISH data could be explained by different growth advantages of the putative subclones resulting in clonal selection in case of CCA procedure as well as by the much higher representation of the targeted iFISH study.…”

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

“…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]. Table 1 Clones involving chromosomes 4, 6, 10, and 17 at presentation and/or during the course of disease in ten patients with high hyperdiploid acute lymphoblastic leukemia, expressed as percentages (13) 29 (13) 24 (15) 13 (8) 18 (15) 44 (34) 6 (3) 8 (5) 19 (16) 40 (25) 7 (7) 3 (3) 20 (13) 56 (43) 12 (9) 2 (1) 8 (5) 7 (6) Values in parentheses are numbers of very small abnormal clones (<1%).…”

“…Study patients are further detailed in Supplement 1. Four-color I-FISH using centromeric probes specific for chromosomes 4 (p-4n1/4, kindly provided by Prof. Mariano Rocchi, University of Bari, Italy), 6, 10, and 17 (D6Z1, D10Z1, and D17Z1, respectively; American Type Culture Collection, Manassas, VA) was performed as formerly described [4] on 34 bone marrow samples, 5 of which were reported in Talamo et al [7]. Probes were directly labeled by nick translation with four different fluorochromes (Cy3, Cy3.5, DEAC, and FITC).…”

Genomic Heterogeneity in Acute Leukemia

“…As regards the interphase FISH results, on the other hand, it cannot be excluded that cell-to-cell variability may occur in the non-dividing cells of HeH ALL without being detectable on the cytogenetic level. In line with this, Blandin et al [2008] and Talamo et al [2010] also have reported high frequencies of cell-to-cell variation in HeH cases with interphase FISH. It should be noted, however, that the method of interphase FISH is dependent on correct determination of cut-off values of the used probes to avoid false-positive results.…”