H396P mutation in chronic myeloid leukaemia patient on nilotinib – A case report
- Author:
Nor Syazana Jamali
1
Author Information
1. Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur.
- Publication Type:Case Reports
- Keywords:
Chronic myeloid leukaemia;
mutation analysis;
H396P mutation;
treatment failure;
BCR-ABL1
- From:The Malaysian Journal of Pathology
2021;43(1):63-68
- CountryMalaysia
- Language:English
-
Abstract:
Introduction: The advent of BCR-ABL1-targeted therapy with the tyrosine kinase inhibitor (TKI),
for example, imatinib and nilotinib, marked a turning point in the therapy of chronic myeloid
leukaemia (CML). However, a substantial proportion of patients experience primary or secondary
disease resistance to TKI. There are multifactorial causes contributing to the treatment failure of
which BCR-ABL1 kinase domain mutation being the most common. Here, we describe a case of a
CML patient with H396P mutation following treatment with nilotinib.
Case: A 60-year-old woman presented with abdominal discomfort and hyperleukocytosis. She was
diagnosed as CML in the chronic phase with positive BCR-ABL1 transcripts. Due to the failure to
obtain an optimal response with imatinib treatment, it was switched to nilotinib. She responded
well to nilotinib initially and achieved complete haematological and cytogenetic responses, with
undetectable BCR-ABL1 transcripts. However, in 4 years she developed molecular relapse. Mutation
analysis which was done 70 months after commencement of nilotinib showed the presence of BCRABL1 kinase domain mutation with nucleotide substitution at position 1187 from Histidine(H) to
Proline(P) (H396P). Currently, she is on nilotinib 400mg twice daily. Her latest molecular analysis
showed the presence of residual BCR-ABL1 transcripts at 0.22 %. Discussion/conclusion: This
case illustrates the importance of BCR-ABL1 mutation analysis in CML patients with persistent
BCR-ABL1 positivity in spite of treatment. Early detection and identification of the type of BCRABL1 mutation are important to guide appropriate treatment options as different mutation will have
different sensitivity to TKI.
- Full text:5.2021my01110.pdf
