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Introduction to Myeloproliferative Neoplasms
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
PDGFRA (chromosome 4q12) and PDGFRB (chromosome 5q31–32) are involved in mutations occurring in chronic MPNs. Activating PDGFRA mutations due to FIP1L1–PDGFRA fusion has been described in the subset of patients with SM associated with eosinophilia and HES/CEL [18,19,40,41]. FIP1L1–PDGFRA fusion results from karyotypically occult interstitial deletion of part of chromosome 4, del(4)(q12). PDGFRA mutations can be identified by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR; CHIC2 deletion can serve as a surrogate marker for FIP1L1–PDGFRA fusion) [40]. Patients with these mutations are sensitive to imatinib treatment (although not all patients with SM with eosinophilia respond to imatinib and subset of patients responding to imatinib lack FIP1L1–PDGFRA fusion) [40,42,43]. Other rearrangements involving PDGFRA described in MPNs include t(4;22)(q12;q11) (BCR–PDGFRA), t(4;10)(q12;p11) (KIF5B–PDGFRA), and ins(9;4)(q33;q12q25) (CDK5RAP2–PDGFRA) [44–46].
Primary Eosinophilic Disorders
Published in Richard T. Silver, Ayalew Tefferi, Myeloproliferative Disorders, 2007
Animesh Pardanani, Ayalew Tefferi
PDGFRA can also be activated by chromosomal translocations (Table 3); examples include KIF5B-PDGFRA, t(4:10)(q12;p11) (101), BCR-PDGFRA, t(4;22)(q12;q11) (35), and CDK5RAP2-PDGFRA, ins(9;4)(q33;q12q25) (102).
The evolution in our understanding of the genetics of rheumatoid arthritis and the impact on novel drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Filip Machaj, Jakub Rosik, Bartosz Szostak, Andrzej Pawlik
Since this study, several other RA susceptibility risk loci have been identified e.g. 22q12 [35], BACH2 [36], CDK5RAP2 and DPP4 [37]. A number of studies focusing on the interactions between high-risk HLA variants and low-risk SNPs have demonstrated synergistic effects between the HLA-DRB1 SE alleles and variants in PTPN22, HTR2A and MAP2K4 with regard to an elevated risk of ACPA-positive RA. The combination of risk factors yielded a greater odds ratio than their additive separate effects [21,38,39].