Acute Undifferentiated Leukemia With a Balanced t(5;10)(q35;p12) Resulting in Fusion of HNRNPH1 With MLLT10

Background/Aim: Acute undifferentiated leukemia (AUL) is leukemia which does not express lineagespecific antigens. Such cases are rare, accounting for 2.7% of all acute leukemia. The reported genetic information of AULs is limited to less than 100 cases with abnormal karyotypes and a few cases carrying chimeric genes or point mutation of a gene. We herein present the genetic findings and clinical features of a case of AUL. Case Report: Bone marrow cells obtained at diagnosis from a 31-year-old patient with AUL were genetically investigated. G-Banding karyotyping revealed an abnormal karyotype: comparative genomic hybridization examination confirmed the del(12)(p13) seen by G-banding but also detected additional losses from 1q, 17q, Xp, and Xq corresponding to the deletion of approximately 150 genes from these five chromosome arms. RNA sequencing detected six HNRNPH1::MLLT10 and four MLLT10::HNRNPH1 chimeric transcripts, later confirmed by reverse-transcription polymerase chain reaction together with Sanger sequencing. Fluorescence in situ hybridization analysis showed the presence of HNRNPH1::MLLT10 and MLLT10::HNRNPH1 chimeric genes. Conclusion: To the best of our knowledge, this is the first AUL in which a balanced t(5;10)(q35;p12) leading to fusion of HNRNPH1 with MLLT10 has been detected. The relative leukemogenic importance of the chimeras and gene losses cannot be reliably assessed, but both mechanisms were probably important in the development of AUL.Acute undifferentiated leukemias (AULs) do not express lineage-specific antigens inasmuch as they lack the T-cell lineage marker cytoplasmic CD3, the myeloid marker myeloperoxidase, and B-cell markers (1). AULs account for only 2.7% of acute leukemias, corresponding to an incidence of 1.6 cases per 1,000,000 person-years (2, 3). Age is a very strong predictor for overall survival, with adult patients with AUL faring much worse than do children (3). Genetic information on AULs is limited: The Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (last updated on January 19, 2023) contains 82 AULs with an abnormal karyotype (4). By comparison, the same database contains 21,738 entries on acute myeloid leukemia (AML) and 12,339 entries on acute lymphoblastic leukemia (ALL) with abnormal karyotypes. The following fusion genes have been reported in AUL: BCR::ABL1 (5, 6), ETV6::ABL1 (7), EWSR1::ZNF384 (8), KMT2A::FOXO3 (9), KMT2A::GIMAP8 (10), KMT2A::GPHN (11), KMT2A::MLLT10 (12), and SET::NUP214 (13, 14). In a recent study, mutations of PHF6, SRSF2, RUNX1, and ASXL1 were found in 33%, 40%, 46%, and 33% of examined AUL cases, respectively (15). We herein present the acquired chromosomal aberrations, the presence of a fusion gene, and the heterozygous losses of many gene loci in the bone marrow cells, together with the clinical features, of a patient with acute undifferentiated leukemia.