Assessing efficacy in myelofibrosis treatment: a focus on JAK inhibition

Figures & data

Figure 1. The JAK-STAT signaling pathway.

Cytokines and growth factors bind to the extracellular receptor and induce a series of intracellular changes: (1) JAK proteins associate with the intracellular portion of the receptor and are phosphorylated; (2) phosphorylated JAK proteins in turn phosphorylate STAT proteins, which then phosphorylate other downstream proteins and (3) phosphorylated STAT translocates into the nucleus and promotes the transcription of genes. Other proteins also regulate this signaling pathway, such as SOCS1, which prevents activation of this pathway.

Reproduced with permission from [41].

Table 1. Delphi expert consensus panel definitions of red blood cell transfusion dependence and red blood cell transfusion independence.

	RBC transfusions	Surveillance interval
RBC transfusion dependence	≥2 U/month	3 months
RBC transfusion independence	None	3 months
Reduced RBC transfusion dependence	50% decrease	3 months

RBC: Red blood cell.

Reproduced with permission from [31,33]

Table 2. JAK inhibitors approved and in development.

JAK inhibitors	Stage of clinical development
CYT387	Phase II
LY2784544	Phase I
Pacritinib (SB1518)	Phase I/II
Ruxolitinib	Approved, Phase III
SAR302503	Phase III

Data taken from [102].

Quintás-Cardama A, Kantarjian H, Cortes J, Verstovsek S. Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat. Rev. Drug Discov. 10(2), 127–140 (2011).

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