ABSTRACT
Mastocytosis is no longer considered a subgroup of MPN and will be discussed in Chapter 28.
Chromosomal and Molecular Abnormalities e most common chromosomal anomalies among MPNs in order of frequency are t(9;22)(q34;q11.2), –Y, +8, +9, –7, del(20) (q11q13), del(13)(q12q14), del(5)(q13q33), and del(12)(p12) [2-4]. CML is associated with t(9;22)(q34;q11.2)/Philadelphia chromosome resulting in BCR-ABL1 fusion. e diagnosis of other MPNs requires the absence of BCR/ABL1. Janus kinase 2 (JAK2) V617F mutation occurs in ~95% of patients with PV and in 50% to 60% of those with ET or PMF. Somatic mutations of JAK2 exon 12 are found in PV, and activating mutations of the thrombopoietin receptor gene PML are present in 5% to 10% of patients with ET or PMF with non-mutated JAK2. Mutations of the calreticulin gene (CALR) occur in JAK2-and MPL-ET or PMF (they do not occur in PV). Somatic mutations in other genes, such as TET2, CBL, EZH2, DNMT3A, and ASXL1 are also present in MPNs but are not specic, as they occur in other myeloid malignancies (including myelodysplastic syndrome [MDS] cases). SETBP1 mutations occur in 9% of MDS/MPN and in 4% of MPN cases and are strongly associated with atypical CML (aCML). e concomitant occurrence of a JAK2 (V617) mutation and BCR-ABL1 fusion is rare [5,6]. Pieri et al. found 8 out of 314 patients with typical BCR-ABL+ CML to have mutated JAK2V617 (2.55%) [6]. One of those patients had prior diagnosis of PV, one patient had history of persistent thrombocytosis, and one patient was initially diagnosed with CML and was treated with Imatinib but had persistent thrombocytosis (suggesting of proliferative competition between the JAK2+ clone and the BCR-ABL+ clones, the latter partially controlled by imatinib) [6]. e remaining patients did not present specic clinical features of a BCR-ABL1-MPN, indicating the predominance of clinical phenotype of BCR-ABL1 rearranged CML in those double mutated patients.
