MULTIPLE PATHWAYS drive myelofibrosis progression¹

Pathways include JAK/STAT, BCL-2 family, epigenetic regulators, PI3K, and RAF/MEK/ERK (MAPK)^1,2

• Targeting the JAK/STAT pathway alone may still permit malignant stem cells to evade apoptosis and the disease to progress^2,3
• Additional pathways allow the continued survival of malignant clones that drive disease progression^3,4

• BCL-XL and MCL-1 are the main pro-survival proteins expressed in myelofibrosis, leading to apoptosis resistance¹⁴

• BCL-XL and MCL-1, as well as other anti-apoptotic BCL-2–family proteins, remain active and may contribute to MF progression^6,14,15

AKT=protein kinase B; BCL-2=B-cell lymphoma 2; BCL-XL=B-cell lymphoma-extra large; ERK=extracellular-signal–regulated kinase; JAK=Janus kinase; JAK/STAT=Janus kinase signal transducer and activator of transcription; MAPK=mitogen-activated protein kinase; MCL-1=myeloid cell leukemia-1; MEK=MAPK/ERK kinase; MF=myelofibrosis; mTOR=mammalian target of rapamycin; PI3K=phosphoinositide 3-kinase; RAF=rapidly accelerated fibrosarcoma.

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