LQCL2513 - CMLE - An Unusual JAK2 Mutation Affects the Detection Sensitivity of Allele-Specific Quantitative Polymerase Chain Reaction (AS-qPCR) Assay-LQCL2513

LQCL2513 - Educational Activity

Pdf Summary

The document is a comprehensive case study and educational resource on molecular pathology, focusing on the genetics of myeloproliferative neoplasms (MPN). The material is authored by Linsheng Zhang, MD, PhD from Emory University School of Medicine and is part of a series by ASCP LabQ for 2025. The primary learning objectives include identifying common driver mutations in MPNs, understanding their pathophysiology, explaining allele-specific quantitative polymerase chain reaction (AS-qPCR) for mutation detection, and managing unusual results from these tests.<br /><br />The case study involves a 68-year-old female with clinical signs suggestive of MPN, confirmed through laboratory tests showing neutrophilia and thrombocytosis. Advanced diagnostic tests, including bone marrow biopsy, chromosomal analysis, and next-generation sequencing (NGS), identified a JAK2 V617F mutation, aiding in the diagnosis of BCR::ABL1 negative MPN. This case illustrates the complexity of JAK2 mutations, particularly its challenging detection when atypical mutations occur. The document explains the mechanics of AS-qPCR and its limitations, recommending NGS for complex mutation profiling due to its sensitivity and comprehensiveness.<br /><br />The educational content emphasizes the importance of detecting driver mutations in MPNs like JAK2, CALR, and MPL, discussing the predominant JAK2 V617F mutation and how it alters cellular signaling pathways. The case further discusses how atypical mutations can escape detection through conventional methods, necessitating broader sequencing techniques like NGS for accurate diagnosis. The summary reinforces the indispensability of mutation detection in guiding MPN diagnosis and treatment decisions, highlighting instances where sequencing-based tests provide a more reliable approach for definitive diagnosis.

Keywords

molecular pathology

myeloproliferative neoplasms

JAK2 V617F mutation

AS-qPCR

next-generation sequencing

driver mutations

BCR::ABL1 negative

mutation detection

diagnostic tests

cellular signaling pathways