Contributions
Abstract: EP1069
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Biology & Translational Research
Background
The myeloproliferative neoplasms (MPN) - polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) - are clonal hematopoietic stemcell disorders with acquired genetic mutations JAK2, CALR, and MPL, that constitutively activate the signal-transduction pathways. Recently, non-driver mutations in TET2, ASXL1, SRSF1 and U2AF1 were reported to be associated with the intiation and disease transformation, independent of the driver mutations in myeloproliferatuve neoplasms.
Aims
To define the genomic landscape of non-driver mutations in myeloproliferative neoplasms.
Methods
This study was conducted at Department of Pathology StanfordUniversity from April 2017 to January 2018. We studied the association of non-driver mutations with the presenting clinical and laboratory characteristics in a cohort of 71 subjects of MPN at the time of diagnosis including 15 polycythemia vera, 17 essential thrombocytosis and 39 subjects of primary myelofibrosis. We used targeted next generation sequencing panel (Illumina) to detect somantic mutations in 54 genes. Genomic DNA was extracted from peripheral blood or bone marrow. Libraries were prepared and sequencing performed on MiSeq. NextGen analysis software was used for alignment, variant calling, annotation and reporting.
Results
Among 71 patients 55(77%) harbored JAK2, 9(13%) CALR and 2(3%) MPL mutations while 5(7%) were triple negative. 36(51%) subjects had driver mutations JAK2, CALR and MPL with co-occuring non-driver mutations in PV, ET and PMF subjects (14 vs 17 vs 69%; P=0.001) at the time of diagnosis. The most frequent non-driver mutations are involved in epigenetic regulation, splicing, and signaling like TET2(23%), ASXL1(15%), SRSF2(13%) and U2AF1(7%) being most prevalent in PMF with leukemic transformation (69%; P=0.02). The results also indicate that MPNs primarily affects older male patients (median; 66 yrs, male; 69%). At initial diagnosis 36% displayed transfusion required anemia and 56% constitutional symptoms.
Conclusion
Targeted NGS has become more widely available for the detection of specific MPN associated mutations, allowing early detection of residual disease and leukemic transformation which in turn should lead to improved clinical outcomes for patients by early therapeutic intervention. We further conclude that MPNs have frequent presence of co-occuring non driver mutations, reported in literature to play a key role in the disease initiation, progression and prognosis.
Keyword(s): Myeloproliferative disorder
Abstract: EP1069
Type: E-Poster Presentation
Session title: Myeloproliferative neoplasms - Biology & Translational Research
Background
The myeloproliferative neoplasms (MPN) - polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) - are clonal hematopoietic stemcell disorders with acquired genetic mutations JAK2, CALR, and MPL, that constitutively activate the signal-transduction pathways. Recently, non-driver mutations in TET2, ASXL1, SRSF1 and U2AF1 were reported to be associated with the intiation and disease transformation, independent of the driver mutations in myeloproliferatuve neoplasms.
Aims
To define the genomic landscape of non-driver mutations in myeloproliferative neoplasms.
Methods
This study was conducted at Department of Pathology StanfordUniversity from April 2017 to January 2018. We studied the association of non-driver mutations with the presenting clinical and laboratory characteristics in a cohort of 71 subjects of MPN at the time of diagnosis including 15 polycythemia vera, 17 essential thrombocytosis and 39 subjects of primary myelofibrosis. We used targeted next generation sequencing panel (Illumina) to detect somantic mutations in 54 genes. Genomic DNA was extracted from peripheral blood or bone marrow. Libraries were prepared and sequencing performed on MiSeq. NextGen analysis software was used for alignment, variant calling, annotation and reporting.
Results
Among 71 patients 55(77%) harbored JAK2, 9(13%) CALR and 2(3%) MPL mutations while 5(7%) were triple negative. 36(51%) subjects had driver mutations JAK2, CALR and MPL with co-occuring non-driver mutations in PV, ET and PMF subjects (14 vs 17 vs 69%; P=0.001) at the time of diagnosis. The most frequent non-driver mutations are involved in epigenetic regulation, splicing, and signaling like TET2(23%), ASXL1(15%), SRSF2(13%) and U2AF1(7%) being most prevalent in PMF with leukemic transformation (69%; P=0.02). The results also indicate that MPNs primarily affects older male patients (median; 66 yrs, male; 69%). At initial diagnosis 36% displayed transfusion required anemia and 56% constitutional symptoms.
Conclusion
Targeted NGS has become more widely available for the detection of specific MPN associated mutations, allowing early detection of residual disease and leukemic transformation which in turn should lead to improved clinical outcomes for patients by early therapeutic intervention. We further conclude that MPNs have frequent presence of co-occuring non driver mutations, reported in literature to play a key role in the disease initiation, progression and prognosis.
Keyword(s): Myeloproliferative disorder