Association of JAK2 Mutation Status and Cytogenetic Abnormalities in Myeloproliferative Neoplasms and Myelodysplastic/Myeloproliferative Neoplasms

Abstract

Myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms are heterogeneous disorders. JAK2 mutation testing and karyotyping are routinely used for diagnosis but have not been incorporated into risk stratification in Philadelphia chromosome-negative myeloproliferative neoplasms. This study correlated cytogenetic abnormalities with disease stage and JAK2 status. A total of 179 cases were analyzed for the JAK2 mutation. Among them, cytogenetic data were available for 97 cases-45 of 106 JAK2+ and 52 of 73 JAK2-. The JAK2+ group showed a higher frequency of cytogenetic anomalies than the JAK2- group (23/45 [51%] vs 14/52 [27%]). Chromosome 9, chromosome 7, and 20q- were recurrent abnormalities in the JAK2+ group, whereas 13q- and trisomy 21 were common in the JAK2- group. In the JAK2+ group, chromosome 7 and complex cytogenetic abnormalities were associated with excess blasts/blastic transformation (P < .05), whereas no cases with 20q- underwent blastic transformation. Our results suggest that incorporation of JAK2 mutation testing and karyotyping allows for monitoring of disease progression with prognostic and therapeutic implications.

MYBL2 haploinsufficiency increases susceptibility to age-related haematopoietic neoplasia

“…1 It has been proposed that DNA mutations accumulate during the life of an individual as a consequence of failure to correct errors introduced in the genome during the cell replicative process, leading to either activation of oncogenes or silencing of tumour suppressors that operate as driving factors in the initiation of the disease. 2, 3 Indeed, links have been established between age-related MPNs and specific cytogenetic abnormalities, 4 and older patients with MPN exhibit a higher frequency of chromosomal defects. 5 …”

Detection of mutations in JAK2 exons 12–15 by Sanger sequencing

“…A cytogenetic review of 97 cases revealed a higher frequency of cytogenetic anomalies in MPN patients who were positive for JAK2 mutations as compared to those who were negative (51% vs . 27%) .…”

“…Cytogenetic abnormalities are routinely assessed in MPN patients to establish a diagnosis but not to stratify disease prognosis, and they are not used for risk stratification as in the case of acute myeloid leukemia . The frequency of cytogenetic abnormalities in MPN varies between 3% and 40% depending on the number of patients at different stages of MPN and MDS/MPN that are included in the studies.…”

“…Thus, the p.G571S mutation may induce a conformational change that makes the adjacent Y570 inaccessible and prevents its phosphorylation, yielding a constitutively active JAK2 kinase [23,29]. Cytogenetic abnormalities are routinely assessed in MPN patients to establish a diagnosis but not to stratify disease prognosis, and they are not used for risk stratification as in the case of acute myeloid leukemia [30]. The frequency of cytogenetic abnormalities in MPN varies between 3% and 40% [31,32] depending on the number of patients at different stages of MPN and MDS/MPN that are included in the studies.…”

“…The frequency of cytogenetic abnormalities in MPN varies between 3% and 40% [31,32] depending on the number of patients at different stages of MPN and MDS/MPN that are included in the studies. A cytogenetic review of 97 cases revealed a higher frequency of cytogenetic anomalies in MPN patients who were positive for JAK2 mutations as compared to those who were negative (51% vs. 27%) [30].…”