A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report

Abstract

Background: Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression.

Case presentation: A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died.

Conclusions: To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome.

Keywords: Near-triploidy karyotype; PAX5-SPECC1; TCF3-PBX1; der(9)t(9;17)(p13;q11.2) translocation.

Fig. 1

Karyotype and TCF3-PBX1 confirmation. a Representative GTG-banded metaphase of the leukemic clone at diagnosis and b at relapse. c RT-PCR to TCF3-PBX1 at diagnosis and relapse, respectively. M, marker (100pb); N, negative control; D, diagnosis sample; R, relapse sample. d Sequencing of truncated TCF3-PBX1 at diagnosis and relapse

Fig. 2

Characterization of additional abnormalities identified. a, b MLPA profile of matched sample of case described using the P335 ALL SALSA MLPA kit at diagnosis and relapse sample, respectively. c 3’RACE-PCR PAX5 and sequencing of truncated PAX5 after 3’RACE-PCR with diagnosis sample. M, marker (1 kb); N, negative control; D, diagnosis sample; R, relapse sample. d RT-PCR to PAX5-SPECC1 and sequencing of PAX5 transcript at diagnosis and relapse. e Expected protein sequence of the truncated PAX5 transcript derived from the PAX5-SPECC1 head-to-head fusion. The translated protein refers to the PAX5–201 (NM_016734), showing its alternating exons (black and green) with splice acceptor amino acid residue (red), and amino acid residues coded from the fusion site on SPECC1 (green). f Schematic representation of the PAX5 wild-type protein and the fusion transcript detected