title: Activation of the Janus kinase/signal transducer and activator of transcription pathway in multiple myeloma is not related to point mutations in kinase and pseudokinase domains of JAK1.
abstract: Abstract Considering the recent impact of tyrosine kinase inhibitors in the treatment of myeloproliferative disorders carrying a recurrent JAK2 mutation not identified in multiple myeloma (MM), this study aimed to search for mutations in kinase and pseudokinase domains of the JAK1 gene in an attempt to define any critical and recurring change that can be used as a therapeutic target. We obtained CD138 + purified cells from 27 bone marrow aspirates of untreated MM, four normal controls and four MM cell lines. After amplification of kinase and pseudokinase domains of JAK1 in cDNA samples, the fragments were automatically sequenced. Seventy-eight percent of MM cases showed at least one polymorphism, all being synonymous single nucleotide polymorphisms (SNPs), with allele frequencies consistent with previous studies in normal European, African American and Asian populations. The four cell lines also showed only synonymous SNPs. Mutations in the kinase and pseudokinase domains of the JAK1 gene do not seem to be important for activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway because we were not able to find any recurrent mutation in a case series of 27 patients and four MM cell lines.
authors.affiliation: Federal University of São Paulo, UNIFESP , São Paulo , Brazil.
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Corbi
authors.forename: Mariana Bleker
authors.initials: MB
authors.lastname: de Oliveira
authors.forename: Vania M
authors.initials: VM
authors.lastname: Morelli
authors.forename: Sang W
authors.initials: SW
authors.lastname: Han
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Laurent
authors.initials: L
authors.lastname: Knoops
authors.forename: Gisele W B
authors.initials: GW
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D045744:Cell Line, Tumor; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053613:Janus Kinase 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050791:STAT Transcription Factors; D053613:Janus Kinase 1; D053612:Janus Kinases