PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications
- 1Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA USA
- 2Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY USA
- 3University of Virginia Comprehensive Cancer Center, Charlottesville, VA USA
Abstract
Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies characterized by the overproduction of mature myeloid lineage cells. Although JAK2 inhibitors, such as ruxolitinib, can alleviate constitutional symptoms, they typically fail to eradicate malignant clones or reverse bone marrow fibrosis. Moreover, treatment failure and drug intolerance often limit their long-term use. Recent studies have identified PIM1 kinase as an important mediator of MPN pathogenesis. PIM1 expression is upregulated in MPN hematopoietic progenitors, which may contribute to aberrant proliferation and disease progression by regulating key downstream effectors, including mTORC1, BAD, MYC, HIF-1α, and TGF-β. Notably, PIM1 contributes to JAK2 inhibitor-persistent cell growth, and its inhibition restores ruxolitinib sensitivity in JAK2 mutant cells. Preclinical studies using genetic ablation and pharmacological inhibition of PIM1 have shown significant attenuation of the myelofibrosis phenotype in mouse models, providing a strong rationale for targeting this kinase. PIM kinase inhibitors are currently being evaluated in clinical trials for patients with myelofibrosis. This review summarizes the current understanding of PIM1 biology in the context of MPNs, details the molecular mechanisms underlying its pathogenic contributions, and evaluates the translational potential of PIM1-targeted therapies for MPNs.
Related
- PO030 | PLATELET AGGREGOMETRY AS POTENTIAL TOOL TO EVALUATE ANTI-PLATELET RESPONSE IN MYELOPROLIFERATIVE NEOPLASMS: COMPARISON OF DIFFERENT TECHNIQUES AND INITIAL RESULTS
- The JAK2 V617F revolution in myeloproliferative neoplasms.
- FDX1 is associated with CALR abundance and JAK–STAT-related inflammatory signaling in myeloproliferative neoplasms
- Megakaryocytic proteomic signatures define myeloproliferative neoplasms
- Defining and predicting disease progression in myeloproliferative neoplasms: a proposed biomarker-driven approach
BibTeX
@article{dutta2026pim1,
title = {{PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications}},
author = {Avik Dutta and Lilian Varricchio and Ronald Hoffman and Golam Mohi},
journal = {Leukemia},
year = {2026},
month = sep,
doi = {10.1038/s41375-026-03144-5},
url = {https://doi.org/10.1038/s41375-026-03144-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications
AU - Avik Dutta
AU - Lilian Varricchio
AU - Ronald Hoffman
AU - Golam Mohi
PY - 2026
DA - 2026/09/28
JO - Leukemia
DO - 10.1038/s41375-026-03144-5
UR - https://doi.org/10.1038/s41375-026-03144-5
AB - Myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies characterized by the overproduction of mature myeloid lineage cells. Although JAK2 inhibitors, such as ruxolitinib, can alleviate constitutional symptoms, they typically fail to eradicate malignant clones or reverse bone marrow fibrosis. Moreover, treatment failure and drug intolerance often limit their long-term use. Recent studies have identified PIM1 kinase as an important mediator of MPN pathogenesis. PIM1 expression is upregulated in MPN hematopoietic progenitors, which may contribute to aberrant proliferation and disease progression by regulating key downstream effectors, including mTORC1, BAD, MYC, HIF-1α, and TGF-β. Notably, PIM1 contributes to JAK2 inhibitor-persistent cell growth, and its inhibition restores ruxolitinib sensitivity in JAK2 mutant cells. Preclinical studies using genetic ablation and pharmacological inhibition of PIM1 have shown significant attenuation of the myelofibrosis phenotype in mouse models, providing a strong rationale for targeting this kinase. PIM kinase inhibitors are currently being evaluated in clinical trials for patients with myelofibrosis. This review summarizes the current understanding of PIM1 biology in the context of MPNs, details the molecular mechanisms underlying its pathogenic contributions, and evaluates the translational potential of PIM1-targeted therapies for MPNs.
SN - 0887-6924
SN - 1476-5551
ER -