Vol 3, No 3 (2012)
Review paper
Published online: 2012-10-11
JAK inhibitors — are we witnessing a breakthrough in the treatment of myelofibrosis?
Hematologia 2012;3(3):193-200.
Abstract
Primary myelofibrosis (PMF), a myeloproliferative neoplasm, is manifested by anemia,
leukoerythroblastosis in peripheral blood and extramedullary hematopoiesis. Consitutional
symptoms that result from massive splenomegaly and elevated levels of serum proinflammatory
cytokines are present in some MF cases. 50–60% of patients with myelofibrosis (MF) were
found to have a JAK2V617F point mutation, however dysregulation of JAK-STAT signal
pathway may play a central pathogenic role in MF, regardless of the mutational status of JAK2.
The above-mentioned discovery provided an impetus to the development of JAK inhibitors and
ruxolitinib was the first approved in November 2011 by the Food and Drug Administration for
the treatment of patients with intermediate and high risk myelofibrosis. Ruxolitinib and other JAK inhibitors currently in clinical trials, are found to alleviate constitutional symptoms and
reduce the spleen volume, but have yet to reverse bone marrow fibrosis as well as to improve
survival over best available treatment. Their increased use may be restricted by side effects
particularly anemia and thrombocytopenia. This review presents current data and perspective
of JAK inhibitors; we discussed in details the recently published studies COMFORT-1 and
COMFORT-2 which became the background for ruxolitinib approval.
leukoerythroblastosis in peripheral blood and extramedullary hematopoiesis. Consitutional
symptoms that result from massive splenomegaly and elevated levels of serum proinflammatory
cytokines are present in some MF cases. 50–60% of patients with myelofibrosis (MF) were
found to have a JAK2V617F point mutation, however dysregulation of JAK-STAT signal
pathway may play a central pathogenic role in MF, regardless of the mutational status of JAK2.
The above-mentioned discovery provided an impetus to the development of JAK inhibitors and
ruxolitinib was the first approved in November 2011 by the Food and Drug Administration for
the treatment of patients with intermediate and high risk myelofibrosis. Ruxolitinib and other JAK inhibitors currently in clinical trials, are found to alleviate constitutional symptoms and
reduce the spleen volume, but have yet to reverse bone marrow fibrosis as well as to improve
survival over best available treatment. Their increased use may be restricted by side effects
particularly anemia and thrombocytopenia. This review presents current data and perspective
of JAK inhibitors; we discussed in details the recently published studies COMFORT-1 and
COMFORT-2 which became the background for ruxolitinib approval.
Keywords: primary myelofibrosisJAK2V617FJAK inhibitors
