A 2.5-year-old boy was diagnosed with myeloproliferative disorder and eosinophilia associated with lymphoblastic lymphoma both bearing the CCDC88C-PDGFRB fusion.
Although patients with PDGFRB rearrangement mostly present with myeloproliferative neoplasm and eosinophilia, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) have also been reported in this population.
Myeloproliferative neoplasms associated with FIP1L1-PDGFR rearrangements represent a rare subset of myeloid and lymphoid malignancies, characterised by the presence of eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 genes.
Here, we developed version 2.0 of a genomically based systematic kinase fusion screen and used it to detect a novel imatinib-sensitive C6orf204-PDGFRB fusion in a patient with precursor T lymphoblastic lymphoma (T-ALL) and an associated myeloproliferative neoplasm with eosinophilia.
The introduction of JAK2 mutation testing has changed dramatically the diagnostic algorithms for myeloproliferative neoplasms (MPNs) but there is still a place for conventional cytogenetic analysis in the initial work-up of MPN cases, particularly as this group of myeloid disorders has been expanded to include chronic eosinophilic leukaemia and myeloid neoplasms with abnormalities of the PDGFRA, PDGFRB, and FGFR1 genes.
Important changes include (1) the change of nomenclature of myeloproliferative disorder to myeloproliferative neoplasm emphasizing the clonal nature of these disorders; (2) the classification of mast cell disease as an MPN; (3) the reorganization of the eosinophilic disorders into a molecularly defined category of PDGFRA, PDGFRB and FGFR1-associated myeloid and lymphoid neoplasms with eosinophilia and chronic eosinophilic leukemia, not otherwise specified; and (4) refinement of the diagnostic criteria for PV, ET and PMF incorporating recently described molecular markers, JAK2V617F, JAK2 exon 12 mutations and MPL mutations.
This review highlights the important diagnostic tools in classical and atypical myeloproliferative neoplasms mainly the JAK2V617F mutation, the Mpl receptor, Polycythemia rubra vera 1 (PRV1), platelet-derived growth-factor receptor alpha (PDGFRA), platelet-derived growth-factor receptor beta (PDGFRB), fibroblast growth-factor receptor 1 (FGFR1) and c-kit tyrosine kinase.
Quantitative reverse transcriptase polymerase chain reaction analysis is a simple and useful adjunct to standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in eosinophilia-associated myeloproliferative neoplasms or related disorders.
Tel/PDGFRbeta results in constitutive activation of several signaling pathways and induces a myeloproliferative disease in mice, with signals via tyrosines 579/581 identified as being important for this phenotype.
Therapeutically validated oncoproteins in myeloproliferative neoplasms (MPN) include BCR-ABL1 and rearranged PDGFR proteins.The latter are products of intra- (e.g.
Imatinib is usually a highly effective treatment for myeloproliferative neoplasms (MPNs) associated with ABL, PDGFRA or PDGFRB gene fusions; however, occasional imatinib-responsive patients have been reported without abnormalities of these genes.
Myeloid neoplasms are now classified into five categories: acute myeloid leukemia, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN, and myeloid and/or lymphoid malignancies associated with eosinophilia and PDGFR or FGFR1 rearrangements.
Therapeutically validated oncoproteins in myeloproliferative neoplasms (MPNs) include BCR-ABL in chronic myelogenous leukemia (CML) and a spectrum of PDGFRA/B mutant proteins that are products of intra- (eg, FIP1L1-PDGFRA) or interchromosomal (eg, ETV6-PDGFRB) gene fusions.
Fusion of PRKG2 and SPTBN1 to the platelet-derived growth factor receptor beta gene (PDGFRB) in imatinib-responsive atypical myeloproliferative disorders.
Lack of response to imatinib mesylate in a patient with accelerated phase myeloproliferative disorder with rearrangement of the platelet-derived growth factor receptor beta-gene.
NIN, a gene encoding a CEP110-like centrosomal protein, is fused to PDGFRB in a patient with a t(5;14)(q33;q24) and an imatinib-responsive myeloproliferative disorder.
p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder.
In contrast, control mice coexpressing with TEL-PDGFRB and a DNA-binding-mutant of AE developed a nontransplantable myeloproliferative disease identical to that induced by TEL-PDGFRB alone.