New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases

Abstract

To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

Chromosome abnormalities in advanced stage T‐cell lymphoblastic lymphoma of children and adolescents: a report from Japanese Paediatric Leukaemia/Lymphoma Study Group (JPLSG) and review of the literature

“…We compared the cytogenetic findings in the current study with the published reports from the three largest‐scale studies on T‐LBL (Burkhardt et al , 2006; Lones et al , 2007; Uyttebroeck et al , 2007; Table S3) and those from the two largest‐scale studies on T‐ALL combined (Heerema et al , 1998; Schneider et al , 2000; Table S3) (Table I). The frequencies of almost all of the cytogenetic abnormalities in T‐LBL and T‐ALL had no significant difference, but translocation involving chromosome region 9q34 was significantly more common in T‐LBL than in T‐ALL ( P = 0·0004, Table S3) and translocation t(9;17) was also more common in T‐LBL (4%, 4/92) than in T‐ALL (0%, 0/523, P = 0·0004) (Table I).…”

High‐resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia

“…In addition, differences in culture demands of clones and subclones could skew the pattern of aberrations found by G‐band karyotyping. Accordingly, patients with T‐lineage leukaemia are particularly difficult to karyotype by G‐band karyotyping, and the present study indicates that HRCGH may be especially helpful in the delineation of cytogenetic changes in such patients (17). The 24‐colour FISH technique (spectral karyotyping), which similar to G‐band karyotyping also demands metaphase preparations, could further improve the cytogenetic mapping of these patients by mapping balanced translocations (42).…”

“…Whereas G‐band karyotyping revealed five aberrations including one marker chromosome in three of the 10 T‐lineage leukaemias, HRCGH detected 20 aberrations in eight of the patients. Eighteen of these 20 aberrations have recurrently been found in T‐cell leukaemias (17).…”

Deregulation of cyclin D2 by juxtaposition with T‐cell receptor alpha/delta locus in t(12;14)(p13;q11)‐positive childhood T‐cell acute lymphoblastic leukemia

“…Hence, somatic rearrangements of TRA@ lead to a deletion of TRD@ (16). BPs within the TRA@/TRD@ locus occur in more than 20% of T‐ALLs with abnormal karyotypes (17), and the mechanisms underlying these translocations most likely involve illegitimate V(D)J recombination. Translocations within the TRA@/TRD@ locus may affect the expression of the target gene both on the der(14), as TLX1 in t(10;14)(q24;q11) (18), or on the non‐der(14), as OLIG2 in t(14;21)(q11;q22) (19) and – as shown here – CCND2 in t(12;14)(p13;q11).…”