We also discuss the role of JAK inhibitors for treatment of CSF3RT618I-mutated chronic neutrophilic leukemia and hematologic malignancies with rearranged JAK2 gene.
With the discoveries of underlying mutations in JAK2, MPL, and, most recently, calreticulin (CALR), that together account for ∼90% of patients with MPNs, these conditions are now among the best characterized of hematological malignancies.
Although multiple mutations within JAK2, which abrogate the function of JH2 and sustain JAK2 activation, are widely observed in hematological malignancies, comparable mutations have not been detected in solid tumors.
Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic malignancies.
However it is not so easy, because iPSCs from hematological malignancies have been established only from myeloproliferative neoplasms including chronic myelogenous leukemia (CML) and JAK2-V617F mutation-positive polycythemia vera (PV). iPSC technology has great potential to promote oncology research based on patient samples.
While activation of STAT3 is commonly achieved by somatic mutations to JAK2 in hematologic malignancies, similar mutations are not often found in solid tumors.
Myeloproliferative neoplasms (MPN) are clonal hematological malignancies that are frequently -associated with an acquired somatic mutation in JAK2 (JAK2V617F).
Alterations of the short arm of chromosome 12 (12p) occur in various hematologic malignancies and ETV6 and CDKN1B, which are located on 12p, have been implicated as leukemogenic genes of interest.
The diagnostic value of JAK2 mutational analysis in myeloproliferative neoplasms (MPN) is now well established and endorsed by the World Health Organization classification system for hematologic malignancies.
This case reiterates the importance of correlating morphologic and phenotypic findings with the results of cytogenetic analysis to avoid errors in diagnosing hematologic neoplasms and highlights the rare association of B-cell non-Hodgkin lymphoma with aberrations of TEL.
By reviewing these specific areas, we hope to have a better understanding of Jak2's role in hematologic malignancies and to shed light on the utility of Jak2 inhibitors.
The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F).