Concomitant L248V With E225V Mutation in the BCR-ABL Gene Associated With Rapid Chronic Myeloid Leukemia Lymphoid Blast Crisis

TL;DR

A 40-year-old woman with chronic myeloid leukemia developed a sudden lymphoid blast crisis linked to specific mutations in the BCR-ABL gene.

Contribution

This is the first reported case of concomitant L248V and E225V mutations with partial exon 4 deletion in the BCR-ABL1 gene causing a lymphoid blast crisis.

Findings

The patient developed a sudden lymphoid blast crisis after five months of imatinib treatment.

Molecular analysis revealed concomitant L248V and E225V mutations with partial exon 4 deletion in the BCR-ABL1 gene.

The patient was treated with intensive chemotherapy and dasatinib following the crisis.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome (Ph), resulting from the t(9;22)(q34;q11.2) translocation. Imatinib, a tyrosine kinase inhibitor (TKI), has revolutionized the treatment of CML. However, despite the initial response, some patients may progress to an advanced stage, such as a blast crisis.

We report a 40-year-old female who presented with CML chronic phase (CP) taking imatinib 400 mg/day and achieved a complete hematological response (CHR) after one month of treatment. She achieved a suboptimal response in the third month (BCR-ABL positive 10.29% IS). However, five months into therapy, she developed a sudden lymphoid blast crisis with chromosomal aberrations involving chromosomes 10 and 12. Molecular analysis detected concomitant L248V with partial exon 4 deletion and E225V mutations within the BCR-ABL1 fusion gene. The patient received intensive chemotherapy and dasatinib.

We report the first case of concomitant mutation of L248V with partial exon 4 deletion and E255V on BCR-ABL1 gene mutation, which contributes to a sudden precursor B-cell lymphoid blast crisis.

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