ABSTRACT
While our understanding of the molecular basis of mixed phenotype acute leukemia (MPAL) has progressed over the decades, our knowledge is limited and the prognosis remains poor. Investigating cases of familial leukemia can provide insights into the role of genetic and environmental factors in leukemogenesis. Although familial cases and associated mutations have been identified in some leukemias, familial occurrence of MPAL has never been reported. Here, we report the first cases of MPAL in a family. A 68-year-old woman was diagnosed with MPAL and received haploidentical stem cell transplantation from her 44-year-old son. In four years, the son himself developed MPAL. Both cases exhibited similar characteristics such as biphenotypic leukemia with B/myeloid cell antigens, Philadelphia translocation (BCR-ABL1 mutation), and response to acute lymphoblastic leukemia-type chemotherapy. These similarities suggest the presence of hereditary factors contributing to the development of MPAL. Targeted sequencing identified shared germline variants in these cases; however, in silico analyses did not strongly support their pathogenicity. Intriguingly, when the son developed MPAL, the mother did not develop donor-derived leukemia and remained in remission. Our cases provide valuable insights to guide future research on familial MPAL.
Subject(s)
Leukemia, Biphenotypic, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Female , Aged , Adult , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Acute Disease , Phenotype , Germ Cells , Leukemia, Biphenotypic, Acute/genetics , Leukemia, Biphenotypic, Acute/therapy , Leukemia, Biphenotypic, Acute/diagnosisABSTRACT
Pulmonary embolism and deep venous thrombosis (PE/DVT) are well-known lethal complications in autoimmune hemolytic anemia (AIHA). However, the impact of their treatment is unclear. Here, we describe three elderly Japanese patients with AIHA who developed PE/DVT early after glucocorticoid administration. All patients presented with active hemolysis and high D-dimer levels upon admission. Thromboembolism was confirmed within 2 weeks after starting glucocorticoid, suggesting that both active hemolysis and glucocorticoid administration synergistically contributed to the development of PE/DVT. Clinicians should consider that such synergism may increase the risk of thromboembolism in patients with AIHA, and prophylactic anticoagulation is worth considering in patients after starting glucocorticoid.
