Genetic and Clinical Progression of MYSM1 Related Bone Marrow Failure into Myeloid Malignancies: Case Series and Review of Literature

MYSM1, located on chromosome 1p32.1, encodes histone H2A deubiquitinase, a transcription regulator involved in DNA damage response. Biallelic MYSM1 variants are linked to rare bone marrow failure syndromes, presenting with cytopenia, B-cell deficiency, hypogammaglobulinemia, and developmental abnormalities. We report four cases of MYSM1 mutations progressing from marrow failure to MDS or AML within 9-10 years. Genetic abnormalities, including TP53 mutation and chromosomal anomalies, suggest clonal evolution. Hematopoietic stem cell transplantation achieved remission in two patients with adverse cytogenetics. Further research is needed to refine management strategies and assess long-term outcomes in MYSM1-associated marrow failure and MDS.