The t(1;9)(p34;q34) fusing ABL1 with SFPQ, a pre-mRNA processing gene, is recurrent in acute lymphoblastic leukemias

Commonly altered genomic regions in acute myeloid leukemia are enriched for somatic mutations involved in chromatin remodeling and splicing

“…In cancer, SFPQ has been shown to be translocated to TFE3 and ABL in papillary renal cell carcinoma and in B-cell progenitor ALL, respectively. 44,45 Thus, mutated SFPQ might play a significant role in deregulation of splicing in leukemic cells, especially as depletion in SFPQ also inhibits formation of the early spliceosome. 28,46 Screening of AMLs derived from MDS revealed mutations of splicing-associated genes in ϳ 26% of the cases, whereas at the same time only ϳ 7% of de novo AML had mutations in 1 of the 8 splicing factors analyzed.…”

Dasatinib and allogeneic stem cell transplantation enable sustained response in an elderly patient with RCSD1-ABL1 -positive acute lymphoblastic leukemia

“…[2][3][4] Here, the RCSD1-ABL1 rearrangement is characterized by the fusion of the N-terminal portion of the RCSD1 gene to ABL1 exon 4, a feature unique for the ABL1 fusion partner genes SFPQ and RCSD1. 4 This unusual breakpoint of the ABL1 gene retains only a part of the SRC homology 2 (SH2) domain regulating autophosphorylation, and lacks the SH3 inhibitory module.…”

“…[2][3][4] Here, the RCSD1-ABL1 rearrangement is characterized by the fusion of the N-terminal portion of the RCSD1 gene to ABL1 exon 4, a feature unique for the ABL1 fusion partner genes SFPQ and RCSD1. 4 This unusual breakpoint of the ABL1 gene retains only a part of the SRC homology 2 (SH2) domain regulating autophosphorylation, and lacks the SH3 inhibitory module. 2,4 The RCSD1 gene encodes the phosphoprotein CapZ-interacting protein (CapZIP) that contributes to regulation of actin filament assembly, and is found in immune cells, splenocytes and muscle tissue.…”

“…4 This unusual breakpoint of the ABL1 gene retains only a part of the SRC homology 2 (SH2) domain regulating autophosphorylation, and lacks the SH3 inhibitory module. 2,4 The RCSD1 gene encodes the phosphoprotein CapZ-interacting protein (CapZIP) that contributes to regulation of actin filament assembly, and is found in immune cells, splenocytes and muscle tissue. 5 There is growing evidence that Ph-negative (Ph -) patients showing ABL1 translocations also might benefit from treatment with TKI.…”

Imatinib-induced long-term remission in a relapsed RCSD1-ABL1-positive acute lymphoblastic leukemia

“…Morphological remission was achieved on day 33, although immunoglobulin gene rearrangement-based minimal residual disease (MRD) was still detectable on days 33 and 77 at levels of 10 -3 and 10 -4 , respectively (Figure 2A). After 39 months, the patient experienced a BM relapse with a WBC of 24x10 9 /L and 64% blast cells in the peripheral blood. Therefore, further treatment was initiated according to the ALL-REZ BFM 2002 protocol.…”