The underlying factors driving myelofibrosis
might surprise you.

The impact of driver mutations on the JAK-STAT pathway is well known, but there is more to uncover about myelofibrosis (MF).1 Emerging data have helped identify and validate other somatic mutations, disease phenotypes, and molecular pathways that can impact disease progression. These discoveries help researchers understand why MF may be driven by the JAK-STAT pathway in some patients—but not in all patients.1,2

JAK=janus kinase; STAT=signal transducer and activator of transcription.
SCROLL

The underlying factors driving myelofibrosis
might surprise you.

The impact of driver mutations on the JAK-STAT pathway is well known, but there is more to uncover about myelofibrosis (MF).1 Emerging data have helped identify and validate other somatic mutations, disease phenotypes, and molecular pathways that can impact disease progression. These discoveries help researchers understand why MF may be driven by the JAK-STAT pathway in some patients—but not in all patients.1,2

JAK=janus kinase; STAT=signal transducer and activator of transcription.
 

Primary MF and secondary MF are different at their core.1,2

Primary and secondary MF have certain similarities, but their differences may reveal more about the complexity and severity of primary MF. Taking a closer look at the unique molecular profile of primary MF⁠—⁠including the various driver and high-risk mutations⁠—⁠may provide more insight about chronic inflammation, cytopenias, and the clinical challenges of each patient's case.

Uncover the differences 

Phenotypes have revealed another layer of heterogeneity in MF.2

Cytopenias are just one of several factors that have been shown to define distinct disease phenotypes, each with potentially significant clinical challenges. As researchers investigate these phenotypes and how cytopenias may change over time—whether due to disease progression and/or disease management—they discover what the heterogeneity of MF may reveal about unmet patient needs.

Reveal the distinctions 
Noncytopenic phenotype(typically associatedwith secondary MF)less aggressive + better prognosisCytopenic phenotype(typically associatedwith primary MF)more aggressive + poorer prognosis
JAK-STAT
PATHWAY
RhoA-ROCK
PATHWAY
TLR/IL1R-IRAK1
PATHWAY
FLT3-STAT
PATHWAY
RhoA-ROCK
PATHWAY
TLR/IL1R-IRAK1
PATHWAY
FLT3-STAT
PATHWAY
FLT3-STAT
PATHWAY
RhoA-ROCK
PATHWAY
JAK-STAT
PATHWAY
TLR/IL1R-IRAK1
PATHWAY
JAK-STAT
PATHWAY

There may be more to MF
than the JAK‑STAT pathway.3,4

As research continues to uncover more about the complexity and evolving biology of MF, it reveals the need to look more closely at emerging pathways beyond JAK-STAT. With each pathway discovered, researchers learn more about the need to focus disease management on what may be driving disease progression in each patient.

Explore other pathways 
FLT3=FMS-like tyrosine kinase 3; IL1R=interleukin-1 receptor; IRAK1=interleukin-1 receptor-associated kinase 1; RhoA=Ras homolog family member A; ROCK=rho-associated coiled-coil kinase; TLR=toll-like receptor.
References:
  1. 1. Vainchenker W and Kralovics R. Blood. 2017;129(6):667-679.
  2. 2. Marcellino BK, et al. Clin Lymphoma Myeloma Leuk. 2020;20(7):415-421.
  3. 3. Singer JW, et al. Oncotarget. 2018;9(70):33416-33439.
  4. 4. Naymagon L and Mascarenhas J. HemaSphere. 2017;1(1):e1.