NcXHF

JEAN-JACQUES KILADJIAN
ideal candidates for such strategy. There is evidence to show that
the mutational profıle found in hematopoietic cells has an influence
on treatment effıcacy. For example in ET, patients with or
without a JAK2 mutation display different responses to HU, and
the control of the platelet count requires lower doses of HU in
patients who are positive for JAK2 V617F. 59 In addition, a reduced
prevalence of arterial thrombosis was observed in patients
with a JAK2 V617F–positive status who were receiving
HU compared with anagrelide, whereas no difference was
found in patients with a JAK2 V617F–negative status for the
same endpoint. In PV, IFN-alfa had a differential impact
on malignant clones according to the presence of JAK2 or
TET2 mutations; the JAK2-mutated clones were much
more sensitive to IFN-alfa than the clones with the TET2
mutation. 60 These fındings suggest that the mutational
profıle could provide important information not only in
terms of prognosis but also for the choice of therapy. This
could be particularly important in patients with MF, because
they have a poorer life expectancy and often-complex mutational
profıles. To validate such a personalized approach,
there is a need for prospective studies in cohorts of patients
fully characterized for mutations that may change
the response to therapies. This characterization could be
available soon in a number of centers with the rapid development
and wider availability of next-generation sequencing
techniques.
In terms of new therapies, two classes of drugs currently are
being evaluated in early-phase studies and may play a role in
MPN management in the future. First, histone deacetylase inhibitors
have shown some effıcacy, like panobinostat in PMF 61
or givinostat in PV. 62 The most promising results with these
drugs may result from a combination with JAK inhibitors by
targeting parallel signaling pathways involved in disease development.
A telomerase inhibitor, imetelstat, also has had effıcacy
in ET and PMF and currently is being evaluated for effıcacy and
safety. 63
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: Jean-Jacques Kiladjian, Novartis, Shire.
Consulting or Advisory Role: Jean-Jacques Kiladjian, Novartis, Shire, Incyte. Speakers’ Bureau: None. Research Funding: Jean-Jacques Kiladjian, AOP
Orphan (Inst), Novartis (Inst). Patents, Royalties, or Other Intellectual Property: None. Expert Testimony: None. Travel, Accommodations, Expenses:
Jean-Jacques Kiladjian, Novartis, Incyte. Other Relationships: None.
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