Akira Nishimura, Japan
Tokyo Medical and Dental University Department of Pediatrics and Developmental BiologyPresenter of 1 Presentation
GENOMICS ANALYSIS OF LEUKEMIA PREDISPOSITION IN X-LINKED AGAMMAGLOBULINEMIA
Abstract
Background and Aims
X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by mutations in Bruton's tyrosine kinase (BTK). Because a few XLA patients have been reported with hematological malignancies, we here performed genomic analysis of the tumor cells to investigate whether BTK mutations predispose to this.
Methods
We collected clinical information and samples of two patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and one patient with acute myeloid leukemia (AML). Informed consent for the genetic analysis was obtained from the patients and parents. We performed whole exome sequencing (WES) with a pair of tumor and germline sample in 2 cases of BCP-ALL.
Results
Patient 1 presented with BCP-ALL at 10 years of age following diagnosis with XLA at 3 years of age. He achieved complete remission following chemotherapy. Patient 2 received a diagnosis of XLA at 2 years of age, and developed BCP-ALL at 24 years of age. He underwent allogeneic stem cell transplantation due to minimal residual disease after chemotherapy. Patient 3 was identified to have hypogammaglobulinemia at 5 months of age. He developed AML with myeloid sarcoma at 9 months of age, and was successfully treated with chemotherapy. He was later diagnosed as having XLA. WES revealed a frameshift mutation of MLL2 in Patient 1 and multiple pathogenic mutations including one in TP53 in Patient 2.
Conclusions
These case series identified that germline BTK mutation and additional somatic mutations might induce hematological malignancies in XLA patients.