TY - JOUR
T1 - Mutational profiling in myelofibrosis
T2 - implications for management
AU - Bose, Prithviraj
AU - Verstovsek, Srdan
N1 - Publisher Copyright:
© 2019, Japanese Society of Hematology.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - Mutational profiling, usually by targeted next-generation sequencing, is increasingly performed on patients with myeloproliferative neoplasm-associated myelofibrosis (MF), whether primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF). “Driver” mutations in JAK2, MPL and indels in CALR underlie the vast majority of cases of PMF and post-ET MF; the remainder (≈ 10%) lack identifiable driver mutations, but other clonal markers are usually detectable. Nearly all patients with post-PV MF carry activating JAK2 mutations. In both PMF and post-ET MF, type 1/-like CALR mutations confer a favorable prognosis. Since both type 1/-like and type 2/-like CALR mutations have essentially the same functional consequence, this is a subject of intense research. Additional, “non-driver” mutations, mostly affecting genes encoding epigenetic modifiers or spliceosome components, e.g., ASXL1, EZH2, TET2, DNMT3A, SRSF2 and U2AF1, are frequently found; some of these are associated with inferior survival and have been incorporated into prognostic models. Some mutations, e.g., IDH1/2, are relatively infrequent in chronic phase but are substantially more common in blast phase, and are now therapeutically targetable. While mutational information does not currently influence choice of drug therapy in chronic-phase MF, the presence of a “high molecular risk” genotype is now routinely taken into account for transplant decision-making.
AB - Mutational profiling, usually by targeted next-generation sequencing, is increasingly performed on patients with myeloproliferative neoplasm-associated myelofibrosis (MF), whether primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF). “Driver” mutations in JAK2, MPL and indels in CALR underlie the vast majority of cases of PMF and post-ET MF; the remainder (≈ 10%) lack identifiable driver mutations, but other clonal markers are usually detectable. Nearly all patients with post-PV MF carry activating JAK2 mutations. In both PMF and post-ET MF, type 1/-like CALR mutations confer a favorable prognosis. Since both type 1/-like and type 2/-like CALR mutations have essentially the same functional consequence, this is a subject of intense research. Additional, “non-driver” mutations, mostly affecting genes encoding epigenetic modifiers or spliceosome components, e.g., ASXL1, EZH2, TET2, DNMT3A, SRSF2 and U2AF1, are frequently found; some of these are associated with inferior survival and have been incorporated into prognostic models. Some mutations, e.g., IDH1/2, are relatively infrequent in chronic phase but are substantially more common in blast phase, and are now therapeutically targetable. While mutational information does not currently influence choice of drug therapy in chronic-phase MF, the presence of a “high molecular risk” genotype is now routinely taken into account for transplant decision-making.
KW - Epigenetic
KW - JAK–STAT
KW - Mutations
KW - Myelofibrosis
KW - Splicing
UR - http://www.scopus.com/inward/record.url?scp=85074464049&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85074464049&partnerID=8YFLogxK
U2 - 10.1007/s12185-019-02758-z
DO - 10.1007/s12185-019-02758-z
M3 - Article
C2 - 31630335
AN - SCOPUS:85074464049
SN - 0925-5710
VL - 111
SP - 192
EP - 199
JO - International journal of hematology
JF - International journal of hematology
IS - 2
ER -