CCDC88C‐FLT3 gene fusion in CD34‐positive haematopoietic stem and multilineage cells in myeloid/lymphoid neoplasm with eosinophilia

Abstract

To the Editor, Rearrangements of PDGFRA, PDGFRB, FGFR1 or JAK2 are established features of myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo). 1 The rearrangement of the fms-related tyrosine kinase 3 (FLT3) gene should also be associated with MLN-Eo, and ETV6, SPTBN1, GOLGB1 and TRIP11 have been identified as FLT3 rearrangement partner genes 2 (Figure S1). Cases of MLN-Eo with FLT3 rearrangement are rare but have a poor outcome.We encountered a patient who achieved a favourable long-term outcome by allogeneic haematopoietic stem cell transplantation (allo-HSCT) and without using tyrosine kinase inhibitors, despite being refractory to conventional chemotherapy. The coiled-coil domain containing an 88C (CCDC88C)-FLT3 translocation was identified in this patient who was diagnosed with myeloid neoplasm with T-cell lymphoblastic lymphoma (T-LBL). Chronic myelomonocytic leukaemia (CMML) was one of the differential diagnoses for the current patient; the criteria of chronic myelomonocytic leukaemia included not having the specific genes, such as PDGFRA, if eosinophilia was present. 1 The current case showed a FLT3 rearrangement, and therefore we considered a diagnosis of MLN-Eo as reasonable. The CCDC88C-FLT3 translocation was identified in T-LBL, CD34-positive haematopoietic stem and multilineage cells.We speculated that FLT3 was associated with the t(13;14)(q12;q32) translocation. Previous reports indicated FLT3 breakpoints in theThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Enhancer-driven gene regulatory networks inference from single-cell RNA-seq and ATAC-seq data

“…5E ). CCDC88C encodes Daple, which activates Wnt signaling [ 70 ], reducing apoptosis [ 71 ], and is upregulated in lymphoma/leukemia B cells versus healthy counterparts [ 72 ]. Variation in TF binding to this enhancer was noted among B cell types: TCF7 exclusively in Normal B, with SPI1, TCF12, STAT3, MYF5, NFIC, and NFIB co-binding in Tumor B proliferation and Tumor B cells ( Fig.…”

Enhancer-driven gene regulatory networks inference from single-cell RNA-seq and ATAC-seq data

“…To inspect the impact of TF binding variation on critical gene expression across various B cell types, we concentrated on one marker gene of DSLL, CCDC88C , and one enhancer (chr14-91366590-91389532), through which CCDC88C was regulated by various TFs. As known, Daple (encoded by CCDC88C ) modulates and activates Wnt signaling (75), which decreases the cell apoptosis (76). Additionally, CCDC88C was proved to be up-regulated in diseased B cells in lymphoma/leukemia compared to healthy ones (77).…”

Case Report: Whole genome sequencing identifies CCDC88C as a novel JAK2 fusion partner in pediatric T-cell acute lymphoblastic leukemia

“…CCDC88C protein is highly expressed in B- and T-cell pediatric leukemias ( https://pecan.stjude.cloud/proteinpaint/CCDC88C ). CCDC88C has been reported a handful occasions in hematological malignancies as fusion partner with FLT3 ( 26 ) as well as PDGFRB ( 27 ) including a case report of pediatric patient with a myeloproliferative disorder ( 28 ). It has also been reported as the 5′ fusion partner to PDGFRB in a young adult with Philadelphia-like ALL that responded to imatinib ( 29 ).…”