RCSD1-ABL1-positive B lymphoblastic leukemia is sensitive to dexamethasone and tyrosine kinase inhibitors and rapidly evolves clonally by chromosomal translocations.

Recently, RCSD1 was identified as a novel gene fusion partner of the ABL1 gene. The RCSD1 gene, located at 1q23, is involved in t(1;9)(q23;q34) translocation in acute B lymphoblastic leukemia. Here we describe RCSD1-ABL1-positive B-cell acute lymphoblastic leukemia (ALL) followed by rapid clonal evolution exhibiting three rare reciprocal translocations. We performed breakpoint analysis of the transcript expressed by the RCSD1-ABL1 fusion gene. RT-PCR and sequence analyses detected transcription of a single RCSD1-ABL1 fusion gene variant, which had breakpoints in exon 3 of RCSD1 and exon 4 of ABL1. The RCSD1 portion of the RCSD1-ABL1 fusion transcript consists of exons 1, 2, and 3. Tyrosine kinase inhibitors, imatinib and dasatinib, coadministered with dexamethasone achieved transient clinical effects in the present RCSD1-ABL1-positive ALL. However, leukemic cells rapidly became refractory to this treatment following the subsequent development of three additional reciprocal chromosomal translocations, t(5;16)(q33;q24), dic(18;20)(p11.2;q11.2) and t(10;19)(q24;p13.3). The present RCSD1-ABL1-positive ALL may represent a state of high chromosomal instability.