@Article{crph909,
AUTHOR = {Afolabi, Blessing Opeyemi and Riwaz, Amani and Weerasena, Jagathpriya and Williams, Senani and Denipitiya, Thanuja and Somawardana, Buddhika and Faizan, Mishal and Galhena, Prasanna},
TITLE = {Mutational Analysis of Driver and Non-driver Mutations of Philadelphia Chromosome-negative Myeloproliferative Neoplasms; Diagnosis and Recent Advances in Treatment},
JOURNAL = {Current Research in Public Health},
VOLUME = {3},
YEAR = {2024},
NUMBER = {1},
PAGES = {13-32},
URL = {https://www.scipublications.com/journal/index.php/WJCOR/article/view/909},
ISSN = {2831-5162},
DOI = {10.31586/wjcor.2024.909},
ABSTRACT = {Myeloproliferative neoplasms (MPNs) are hematological disorders affecting myeloid stem cells. They are classified as Philadelphia (Ph) chromosome positive-chronic myeloid leukemia, and Ph-negative polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, juvenile myelomonocytic leukemia, and MPN unclassifiable. This review is mainly focused on the Ph-negative MPNs namely, PV, ET, and PMF. These affect both males and females with a slight male predominance, with patients mainly presenting in the seventh decade. Patients often present with thrombotic events resulting in complications that lower survival rates. The major driver mutations that have been identified in MPNs are JAK2 Exon 14, JAK2 Exon 12, MPL Exon 10, and CALR Exon 9. The importance of these driver mutations gives due recognition to their inclusion into the 2022 diagnostic criteria of the MPN WHO Classification. However, other non-driver mutations have also been reported, especially in triple-negative cases. These mutations lead to downstream constitutive activation of the JAK/STAT signaling pathway, as well as the MAPK, and PI3K/Akt pathways. Insights into the molecular pathogenesis of MPN and its association with JAK2, CALR, and MPL mutations have identified JAK2 as a rational therapeutic target. Thus, as an approach to MPN therapy, JAK2 inhibitors, such as ruxolitinib, have been shown to effectively inhibit JAK2, and are currently in clinical trials in combination with other drug classes. This review comprehensively examines the molecular markers of the main Ph-negative MPNs, as well as diagnosis and treatment options.},
}

%0 Journal Article
%A Afolabi, Blessing Opeyemi
%A Riwaz, Amani
%A Weerasena, Jagathpriya
%A Williams, Senani
%A Denipitiya, Thanuja
%A Somawardana, Buddhika
%A Faizan, Mishal
%A Galhena, Prasanna
%D 2024
%J Current Research in Public Health

%@ 2831-5162
%V 3
%N 1
%P 13-32

%T Mutational Analysis of Driver and Non-driver Mutations of Philadelphia Chromosome-negative Myeloproliferative Neoplasms; Diagnosis and Recent Advances in Treatment
%M doi:10.31586/wjcor.2024.909
%U https://www.scipublications.com/journal/index.php/WJCOR/article/view/909

TY  - JOUR
AU  - Afolabi, Blessing Opeyemi
AU  - Riwaz, Amani
AU  - Weerasena, Jagathpriya
AU  - Williams, Senani
AU  - Denipitiya, Thanuja
AU  - Somawardana, Buddhika
AU  - Faizan, Mishal
AU  - Galhena, Prasanna
TI  - Mutational Analysis of Driver and Non-driver Mutations of Philadelphia Chromosome-negative Myeloproliferative Neoplasms; Diagnosis and Recent Advances in Treatment
T2  - Current Research in Public Health
PY  - 2024
VL  - 3
IS  - 1
SN  - 2831-5162
SP  - 13
EP  - 32
UR  - https://www.scipublications.com/journal/index.php/WJCOR/article/view/909
AB  - Myeloproliferative neoplasms (MPNs) are hematological disorders affecting myeloid stem cells. They are classified as Philadelphia (Ph) chromosome positive-chronic myeloid leukemia, and Ph-negative polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, juvenile myelomonocytic leukemia, and MPN unclassifiable. This review is mainly focused on the Ph-negative MPNs namely, PV, ET, and PMF. These affect both males and females with a slight male predominance, with patients mainly presenting in the seventh decade. Patients often present with thrombotic events resulting in complications that lower survival rates. The major driver mutations that have been identified in MPNs are JAK2 Exon 14, JAK2 Exon 12, MPL Exon 10, and CALR Exon 9. The importance of these driver mutations gives due recognition to their inclusion into the 2022 diagnostic criteria of the MPN WHO Classification. However, other non-driver mutations have also been reported, especially in triple-negative cases. These mutations lead to downstream constitutive activation of the JAK/STAT signaling pathway, as well as the MAPK, and PI3K/Akt pathways. Insights into the molecular pathogenesis of MPN and its association with JAK2, CALR, and MPL mutations have identified JAK2 as a rational therapeutic target. Thus, as an approach to MPN therapy, JAK2 inhibitors, such as ruxolitinib, have been shown to effectively inhibit JAK2, and are currently in clinical trials in combination with other drug classes. This review comprehensively examines the molecular markers of the main Ph-negative MPNs, as well as diagnosis and treatment options.
DO  - Mutational Analysis of Driver and Non-driver Mutations of Philadelphia Chromosome-negative Myeloproliferative Neoplasms; Diagnosis and Recent Advances in Treatment
TI  - 10.31586/wjcor.2024.909
ER  -