Acute lymphoblastic leukemia with the (8;14)(q24;q32) translocation and FAB L3 morphology associated with a B-precursor immunophenotype: the Pediatric Oncology Group experience

Abstract

Five pediatric patients are described with acute lymphoblastic leukemia (ALL) who at presentation had clinical findings suggestive of B cell ALL and lymphoblasts with FAB L3 morphology and the characteristic t(8;14)(q24;q32). However, the leukemia cells of all five patients failed to express surface immunoglobulin (sIg) and kappa or lambda light chains. Based on initial immunophenotyping results consistent with B-precursor ALL, four of these cases were initially treated with conventional ALL chemotherapy. These four patients were switched to B cell ALL treatment protocols once cytogenetic results became available revealing the 8;14 translocation. The fifth case was treated with B cell ALL therapy from the outset. Four of the five patients are in complete remission at 64, 36, 29 and 13 months from diagnosis. One patient relapsed and died 6 months after initial presentation. These five unusual cases with clinical B cell ALL, the t(8;14), and FAB L3 morphology, but negative sIg, demonstrate the importance of careful and multidisciplinary evaluation of leukemic cells with morphology, cytochemistry, immunophenotyping and cytogenetic analysis. Future identification of patients with this profile will allow us to expand our knowledge regarding prognostic significance and optimal treatment for this rare subgroup of patients.

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

“…FISH for c-myc was not performed on the majority of our patients as it is not part of the routine diagnostic work-up of B-ALL cases in our institution. However, previous studies have shown that c-myc rearrangements occur in B-ALL at a very low frequency (0.1-7%) [29][30][31]. Other mechanisms of c-myc upregulation, such as cryptic translocations, genetic changes at the transcriptional level, post-translational modifications or even abnormalities in regulators of c-myc expression, such as BRD4 gene mutations cannot be detected by karyotype or FISH analysis of c-myc and, therefore, cannot be ruled out by conventional cytogenetics.…”

Antigen expression patterns reflecting genotype of acute leukemias

“…There is a strong correlation of MYC translocations with the L3 cytomorphological category. 136,137 Approximately half the patients express CD10 with intensity comparable to that of nonmalignant B-precur- …”

Immunophenotyping of Acute Leukaemias. Immunophänotypisierung akuter Leukämien

“…Do note the exceptions, however, such as paediatric ALL patients with the (8:14) translocation. FAB L3 morphology, and laboratory and clinical features consistent with B cell ALL whose leukaemic blasts showed a less differentiated B-precursor immunophenotype [187] or lacked surface and cytoplasmic Ig [188], and slg lightchain positive adult ALL of LI or L2 morphology without t (8;14) or its variants [189].…”