Volumen: 19 # Number : 1
Publication Date : Enero - Abril Year: 2015
Clinical Significance of Mutations
in BCR-ABL1 Negative Myeloproliferative Neoplasms (MPN).
Authors: Musso, AM
Abstract: JAK2V617F mutation is found in more than 95% of PV
patients and in approximately 60% of patients with ET or
PMF. The presence of this mutation does not appear to
affect the risk of leukemic transformation or survival in
PV or ET. In ET it has been associated with an increased
risk of arterial thrombosis. In PV an increased risk of fibrotic
transformation and cardiovascular events has been
shown when the mutant allele burden is high. In PMF an
increased risk of thrombosis is seen when this mutation
is associated with leucocytosis. JAK2V617F mutation is
found in patients with splanchnic vein thrombosis and
Budd-Chiari syndrome. Lipocalin-2 is overexpressed in
JAK2V617F cells and is responsible for DNA damage
and leukemic transformation. MPLW515L/K are mutations
that induce constitutive activation of the JAK-STAT
pathway, in JAK2V617F negative ET and PMF patients.
CALR mutation can be found in ET and PMF patients,
but not in PV. PMF patients who are “triple negative”, for
JAK2/CALR/MPL mutations, have worse outcome than
patients with CALR type 1 or type 1-like mutations. JAK-
2V617F mutation is found in bone marrow and spleen
progenitor cells of MPN patients. JAK2 inhibitors do not
affect mutated progenitor cells in patients. IFNα treatment
achieves molecular remissions through its effects
on MPN progenitor cells. TET2, ASXL1, IDH1/2, CBL,
IKZF1, LNK, EZH2, TP53 and some other mutations are
investígated in association with MPN.
Key words: Myeloproliferative neoplasms.
Mutations.
Interferon.
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