RCSD1-ABL1 Translocation Associated withIKZF1Gene Deletion in B-Cell Acute Lymphoblastic Leukemia

Abstract

The RCSD1 gene has recently been identified as a novel gene fusion partner of the ABL1 gene in cases of B-cell Acute Lymphoblastic Leukemia (B-ALL). The RCSD1 gene is located at 1q23 and ABL1 is located at 9q34, so that the RCSD1-ABL1 fusion typically arises through a rare reciprocal translocation t(1;9)(q23;q34). Only a small number of RCSD1-ABL1 positive cases of B-ALL have been described in the literature, and the full spectrum of clinical, morphological, immunophenotypic, and molecular features associated with this genetic abnormality has not been defined. We describe extensive genetic characterization of a case of B-ALL with RCSD1-ABL1 fusion, by using conventional cytogenetic analysis, Fluorescence In Situ Hybridization (FISH) studies, and Chromosomal Microarray Analysis (CMA). The use of CMA resulted in detection of an approximately 70 kb deletion at 7p12.2, which caused a disruption of the IKZF1 gene. Deletions and mutations of IKZF1 are recurring abnormalities in B-ALL and are associated with a poor prognosis. Our findings highlight the association of the deletion of IKZF1 gene with the t(1;9)(q24;q34) and illustrate the importance of comprehensive cytogenetic and molecular evaluation for accurate prediction of prognosis in patients with B-cell ALL.

Pan-cancer analysis reveals the relationship between RCSD1 immune infiltration and clinical prognosis in human tumors

“…Through previous studies, we learned that genetic mutations in RCSD1 may induce hematological malignancies ( 33 ), so here, we investigated the type and status of mutation and mutations that may occur in the RCSD1 gene in pan-cancer, and the effect of the RCSD1 gene mutation on patient prognosis. We first analyzed the gene mutation frequency, mutation types, mutation site of RCSD1 in pan-cancer by using the cBioportal web site, RCSD1 mutation rates were found to be high in CHOL, BLCA, LIHC, BRCA, LUAD, SARC, and LUSC.…”

Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL)

“…Case C was a 15-year-old female diagnosed with B-ALL with the t(1;9)(q24;q34.1) shown previously to result in a fusion between the RCSD1 gene (1q24) and the ABL1 gene (9q34.1). [11,15] The patient achieved complete remission upon addition of TKIs to the post-induction chemotherapy regimen, but developed fatal complications after HSCT. Case D was previously described by Raca et al [16] The patient was a 20-year-old male diagnosed with refractory precursor B-ALL with a normal karyotype, in whom CMA analysis revealed a complex rearrangement affecting the long arm of chromosome 1 (1q24.2), with two of the breakpoints occurring within the RCSD1 and ABL2 genes.…”

Detection of a novel SNX2 gene breakpoint in the SNX2::ABL1 fusion transcript in Ph‐like B‐cell acute lymphoblastic leukemia

“…Ph+ B‐ALL patients have an extremely unfavorable prognosis but the development of tyrosine‐kinase inhibitors (TKIs) has significantly improved their early outcome 3 . However, rare ABL1 translocations involve other partners, 4,5 including sorting nexin 2 (SNX2) at 5q23. The SNX2 gene encodes an oligomeric protein that belongs to the SNX family of proteins that are unified by the presence of a phosphoinositide‐binding phox (PX) domain and interact with a number of growth factor receptors, including epidermal growth factor receptor (EGFR) and c‐Met 6,7 .…”