MPLW515L Mutation in Myelofibrosis
Author Information
Author(s): Pikman Yana, Lee Benjamin H, Mercher Thomas, McDowell Elizabeth, Ebert Benjamin L, Gozo Maricel, Cuker Adam, Wernig Gerlinde, Moore Sandra, Galinsky Ilene, DeAngelo Daniel J, Clark Jennifer J, Lee Stephanie J, Golub Todd R, Wadleigh Martha, Gilliland D. Gary, Levine Ross L
Primary Institution: Brigham and Women's Hospital, Harvard Medical School
Hypothesis
We hypothesized that activation of the JAK-STAT pathway might also occur as a consequence of activating mutations in certain hematopoietic-specific cytokine receptors.
Conclusion
Activation of JAK-STAT signaling via MPLW515L is an important pathogenetic event in patients with JAK2V617F-negative myelofibrosis.
Supporting Evidence
- 4 out of 45 patients with JAK2V617F-negative myelofibrosis had the MPLW515L mutation.
- The MPLW515L mutation was not found in any normal samples.
- Expression of MPLW515L in cell lines resulted in cytokine-independent growth.
- Mice with MPLW515L developed a myeloproliferative disorder similar to human myelofibrosis.
Takeaway
Some patients with a blood disease called myelofibrosis have a mutation that makes their blood cells grow too much, which can cause serious health problems.
Methodology
DNA sequence analysis was performed on samples from patients to identify mutations in specific genes related to blood cell development.
Limitations
The statistical power of the analysis was limited by the small number of patients with myelofibrosis in the cohort.
Participant Demographics
Patients with JAK2V617F-negative myelofibrosis.
Digital Object Identifier (DOI)
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