Identification of t(X;1)(q28;q21) generating a novel GATAD2B::MTCP1 gene fusion in CMML and its persistence during progression to AML

Hematological malignancies often involve chromosomal translocations and fusion genes that drive disease progression. While <i>MTCP1</i> is well-known in T-cell prolymphocytic leukemia (T-PLL), its role in myeloid neoplasms is less understood. This report presents the first identification of the t(X;1)(q28;q21) translocation leading to the <i>GATAD2B::MTCP1</i> fusion in acute myeloid leukemia (AML) transformed from chronic myelomonocytic leukemia (CMML). The karyotypes were described according to the International System for Human Cytogenetic Nomenclature 2009. We performed targeted next-generation sequencing (NGS) on a panel of 172 genes commonly mutated in hematological malignancies (Supplemental Table 1), using an Illumina platform. RNA sequencing was conducted on total RNA extracted from bone marrow, also using the Illumina platform. The <i>GATAD2B::MTCP1</i> fusion gene was confirmed by reverse transcription-polymerase chain reaction (RT–PCR) and Sanger sequencing, with specific primers for the fusion transcript (<i>GATAD2B</i>-F: CCTCTTTTTTTCGACGCC; <i>MTCP1</i>-R: ACTGAGCACAACACTTACGC). The <i>GATAD2B::MTCP1</i> fusion results from a breakpoint on 1q21 within <i>GATAD2B</i> exon 1 and Xq28 within <i>MTCP1</i> exon 2. The patient with the <i>GATAD2B::MTCP1</i> fusion exhibited disease progression from CMML to AML. Despite achieving initial remission with venetoclax-based therapy and allo-HSCT, the patient relapsed and died. We propose that the <i>GATAD2B::MTCP1</i> fusion upregulates <i>MTCP1</i> expression rather than generating a fusion protein, thereby contributing to transformation and relapse in AML. Further investigations are needed to elucidate the precise role of this fusion event in myeloid malignancies.