Case Report: Early T-cell precursor acute lymphoblastic leukemia with aberrant CD19 expression and an NPM1 mutation

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a high-risk subtype of T-cell acute lymphoblastic leukemia (T-ALL). Aberrant CD19 expression in ETP-ALL may lead to misdiagnosis of mixed-phenotype acute leukemia. Notably, nucleophosmin 1 (NPM1) mutations, an established molecular hallmark of acute myeloid leukemia (AML), are extremely rare in T-ALL.

We present the case of a 29-year-old male with progressive right retroauricular and cervical lymphadenopathies complicated by severe febrile neutropenia and polymicrobial sepsis. Peripheral blood testing revealed 80% blasts. Bone marrow flow cytometry demonstrated blasts strongly positive for cytoplasmic CD3 and CD7, with aberrant CD19 expression and co-expression of CD34, CD33, and dim cytoplasmic CD79a. The blasts showed dim CD5 expression but were negative for CD1a, CD8, CD10, CD22, and myeloperoxidase, consistent with an ETP-ALL immunophenotype. Next-generation sequencing identified an NPM1 frameshift mutation (p.W288Cfs*12, Type A) and an internal tandem duplication of the Fms-like tyrosine kinase 3 gene (FLT3-ITD), both classic AML-associated mutations. After management of severe sepsis, the patient received three cycles of VHAG (venetoclax, homoharringtonine, cytarabine, and granulocyte colony-stimulating factor)-based chemotherapy followed by haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT). He remained in sustained complete remission at the 7-month follow-up after allo-HSCT.

To our knowledge, this case represents the first reported ETP-ALL with an NPM1 frameshift mutation (p.W288Cfs*12, Type A), which also exhibited aberrant CD19 expression, highlighting the diagnostic challenges posed by unusual immunophenotypic and genomic profiles.