BCR-ABL1 NEGATIVE MYELOPROLIFERATIVE NEOPLASMS
The myeloproliferative neoplasms (MPNs) that are BCR-ABL1 negative include polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF). The diagnosis of MPNs is made by complete blood counts, peripheral smear and bone marrow examination by microscopy and identification of specific molecular markers. >95% of PVs demonstrate either JAK2V617F or JAK2 exon 12 variants. On the other hand, ET and PMF can be caused by variants in JAK2, CALR or MPL genes.
In our laboratory, JAK2V617F is screened by allele specific PCR. CALR defects are screened by fragment analysis for the common 52bp deletion and 5bp insertion variants followed by Sanger sequencing for confirmation. Mutations in exon 12 of JAK2 are screened by Sanger sequencing. MPL mutations in exon 10 are screened by allele specific PCR. MPNs that do not carry mutations in any of these genes are designated as triple-negative MPNs.
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- Linda M. Scott, Wei Tong, et al. JAK2 Exon 12 Mutations in Polycythemia Vera and Idiopathic Erythrocytosis. N Engl J Med 2007; 356:459-468.
- Somatic CALR Mutations in Myeloproliferative Neoplasms with Non-mutated JAK2. Nangalia J, Massie C.E., et al., N Engl J Med. 2013 Dec 19;369 (25):2391-405
- Larissa V. Furtado, Helmut C. Weigelin, Kojo S.J. Elenitoba-Johnson, and Bryan L. Betz Detection of MPL Mutations by a Novel Allele-Specific PCR-Based Strategy The Journal of Molecular Diagnostics, Vol. 15, No. 6, November 2013.