title: Detection of CALR and MPL Mutations in Low Allelic Burden JAK2 V617F Essential Thrombocythemia.
abstract: Myeloproliferative neoplasms are clonal hematopoietic stem cell disorders characterized by aberrant proliferation and an increased tendency toward leukemic transformation. The genes JAK2, MPL, and CALR are frequently altered in these syndromes, and their mutations are often a strong argument for diagnosis. We analyzed the mutational profiles of these three genes in a cohort of 164 suspected myeloproliferative neoplasms. JAK2 V617F mutation was detected by real-time PCR, whereas high-resolution melting analysis followed by Sanger sequencing were used for searching for mutations in JAK2 exon 12, CALR, and MPL. JAK2 V617F mutation was associated with CALR (n = 4) and MPL (n = 4) mutations in 8 of 103 essential thrombocytosis patients. These cases were harboring a JAK2 V617F allelic burden of <4% and a significantly higher platelet count compared with JAK2 V617F (P < 0.001) and CALR (P = 0.001) single-mutation patients. The findings from this study support the possibility of coexisting mutations of the JAK2, CALR, and MPL genes in myeloproliferative neoplasms and suggest that CALR and MPL should be analyzed not only in JAK2-negative patients but also in low V617F mutation patients. Follow-up of these double-mutation cases will be important for determining whether this group of patients presents particular evolution or complications.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Hôpital Nord, Centre Hospitalo-Universitaire de Marseille, Marseille, France; INSERM, UMR_S 1072, Marseille, France; CERBALLIANCE Provence, Marseille, France. Electronic address: fabrice.usseglio@cerballiance.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Usseglio
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Hôpital Nord, Centre Hospitalo-Universitaire de Marseille, Marseille, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Beaufils
authors.affiliation: Hematology Service, Hôpital Pasteur, Centre Hospitalo-Universitaire de Nice, Nice, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Calleja
authors.affiliation: Hematology Service, Hôpital Pasteur, Centre Hospitalo-Universitaire de Nice, Nice, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Raynaud
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Hôpital Nord, Centre Hospitalo-Universitaire de Marseille, Marseille, France; INSERM, UMR_S 1072, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Gabert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D037282:Calreticulin / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D053628:Receptors, Thrombopoietin / Q000235:genetics*; D013920:Thrombocythemia, Essential / Q000235:genetics*; D055815:Young Adult
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2