NcXHF

RISK STRATIFICATION IN PATIENTS WITH MPN
ful addition of cytogenetic abnormalities to risk stratifıcation
for patients with MF recognizes the striking heterogeneity
among patients with this disease at the pathobiologic level,
reflects the remarkable strides made in these now widely
available laboratory assessments, and is in line with prognostic
measurement of other myeloid malignancies (MDS,
AML) that are all now utilizing cytogenetic analysis as a part
of routine risk stratifıcation and treatment decision making.
Besides cytogenetics, it appears that molecular abnormalities
may be crucial to understanding the modern risk stratifıcation
of the patient with MF. 59 More recent discoveries of
the signifıcance of MPL and CALR mutations added to the
already known JAK2 mutation in diagnosis of MF, however,
their signifıcance on risk stratifıcation was unknown until recently.
60 Rumi et al examined the effect of molecular mutations
on outcomes in 617 patients with MF. The authors
found markedly different outcomes based on the molecular
profıle: the longest median overall survival was found in
CALR-mutated (17.7 years), followed by JAK2-mutated (9.2
years), MPL-mutated (9.1 years), and, fınally, a group of patients
termed triple-negative (negative for CALR, JAK2, and
MPL) constituted the poorest-prognosis group with median
overall survival of only 3.2 years.
Other genetic lesions important in MDS and AML have
been identifıed at a relatively high frequency in MF and may
inform risk. For example, mutations in ASXL1 occur in 30%
to 36% of patients with MF. 41 Taking some of these newer
markers into account, further molecular risk stratifıcation
was conducted with inclusion of and assessment of other molecular
mutations commonly found in myeloid malignancies
that are also found in patients with MF: IDH, EZH2, SF3B1,
SRSF2, U2AF1, and ASXL1. 61 Analyses in large MF cohorts
have the power to further refıne prognosis based on genetics,
with a recent study identifying CALR-negative/ASXL1-
positive MF patients exhibiting worse outcomes, suggesting
another higher-risk subset. 62
CONCLUSION
In the 10 years since the discovery of the JAK2V617 mutation
in MPNs, the fıeld has experienced an exponential increase in
terms of clinical and basic science research. With improved
methods of stratifying risk for patients at the clinical, biologic,
cytogenetic, and, now, molecular level, we are entering
a new era of recognizing MPNs total burden of disease, and
we are beginning to consider assigning targeted treatments
based on these assessments. The personalization of MPN diagnosis,
prognosis, and treatment will likely include the congruence
of clinical factors, formal MPN symptom burden
assessment, and cytogenetic and molecular analyses.
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: Alison R. Moliterno, Incyte. Naveen Pemmaraju,
Incyte. Consulting or Advisory Role: Alison R. Moliterno, Incyte. Naveen Pemmaraju, Incyte. Speakers’ Bureau: None. Research Funding: Naveen
Pemmaraju, Novartis. Patents, Royalties, or Other Intellectual Property: None. Expert Testimony: None. Travel, Accommodations, Expenses: None.
Other Relationships: None.
References
1. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib
versus best available therapy for myelofıbrosis. N Engl J Med.
2012;366:787-798.
2. Harrison CN, Mesa RA, Kiladjian JJ, et al. Health-related quality of life
and symptoms in patients with myelofıbrosis treated with ruxolitinib
versus best available therapy. Br J Haematol. 2013;162:229-239.
3. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus
standard therapy for the treatment of polycythemia vera. N Engl J Med.
2015;372:426-435.
4. Kiladjian JJ, Mesa RA, Hoffman R. The renaissance of interferon
therapy for the treatment of myeloid malignancies. Blood. 2011;117:
4706-4715.
5. Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a
induces complete hematologic and molecular responses with low toxicity
in polycythemia vera. Blood. 2008;112:3065-3072.
6. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled
trial of ruxolitinib for myelofıbrosis. N Engl J Med. 2012;366:799-807.
7. Dameshek W. Some speculations on the myeloproliferative syndromes.
Blood. 1951;6:372-375.
8. Rowley JD. Letter: a new consistent chromosomal abnormality in
chronic myelogenous leukaemia identifıed by quinacrine fluorescence
and Giemsa staining. Nature. 1973;243:290-293.
9. James C, Ugo V, Le Couédic JP, et al. A unique clonal JAK2 mutation
leading to constitutive signalling causes polycythaemia vera. Nature.
2005;434:1144-1148.
10. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine
kinase JAK2 in polycythemia vera, essential thrombocythemia,
and myeloid metaplasia with myelofıbrosis. Cancer Cell. 2005;7:387-
397.
11. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine
kinase JAK2 in human myeloproliferative disorders. Lancet.
2005;365:1054-1061.
12. KralovicsR,PassamontiF,BuserAS,etal.Again-of-functionmutationofJAK2
in myeloproliferative disorders. N Engl J Med. 2005;352:1779-1790.
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