Primary myelofibrosis with concurrent MPL and atypical JAK2 mutations

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Myeloproliferative neoplasms (MPNs) are typically diagnosed based on bone marrow morphology.
• Classical driver mutations (JAK2, CALR, MPL) aid in MPN diagnosis and prognosis.
• Dual mutations in MPNs are uncommon, with double mutations in primary myelofibrosis (PMF) being rarely reported.

Purpose of the Study:

• To report two rare cases of primary myelofibrosis (PMF) with concurrent MPL and atypical JAK2 mutations.
• To emphasize the importance of comprehensive molecular profiling in MPN diagnosis.
• To illustrate the dynamic nature of co-mutation emergence during MPN progression.

Main Methods:

• Case report of two PMF patients.
• Detailed analysis of bone marrow morphology.
• Comprehensive molecular profiling to detect driver mutations, including atypical variants.

Main Results:

• Patient 1: MPL (p.W515L) and atypical JAK2 (p.R867Q) mutations, overt fibrotic PMF.
• Patient 2: MPL (p.W515L), atypical JAK2 (p.R683S), and ASXL1 (p.G660Rfs*9) mutations, early fibrotic PMF.
• Both patients presented with thrombocytosis, not leukocytosis, and showed dynamic co-mutation emergence.

Conclusions:

• Concurrent MPL and atypical JAK2 mutations can occur in PMF.
• Broad molecular profiling is crucial for identifying both canonical and atypical mutations in MPNs.
• Detecting co-mutations can inform treatment strategies and improve patient outcomes.