HAEM5:Myeloid/lymphoid neoplasm with PDGFRB rearrangement: Difference between revisions

Patients typically present with splenomegaly; hepatomegaly is less frequent. Lymphadenopathy may also be seen. Skin and cardiac infiltration may be present at diagnosis with resulting cardiac damage. Serum tryptase levels may be elevated.

</blockquote>

==Sites of Involvement==

The mast cells show expression of CD2 and CD25, which is also found in most mast cell disease.

</blockquote>

==Chromosomal Rearrangements (Gene Fusions)==

{| class="wikitable sortable"

|}

</blockquote>

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

Before the introduction of imatinib therapy, the median survival was <2 years. Most patients are now known to have excellent morphologic and molecular response to therapy with a recent study showing a 10-year overall survival of 90%<ref>Cheah CY, Burbury K, Apperley JF, Huguet F, Pitini V, Gardembas M, et al. Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib. Blood. 2014;123(23):3574–7.</ref>. Furthermore, earlier diagnosis due to recognition of this entity will result in earlier initiation of appropriate therapy, preventing cardiac damage and blast phase. Primary and secondary resistance is uncommon; however, initial response typically occurs within 2 months, and if not seen by 3 months, consideration of another therapy is suggested. Whether or not therapy can be stopped in patients with long term molecular remission is still up for debate, with a recent article citing one patient in remission 4 years after therapy cessation<ref>Cerrano M, Crisà E, Gottardi E, Aguzzi C, Boccadoro M, Ferrero D. Long-term therapy-free remission in a patient with platelet-derived growth factor receptor beta (PDGFRB)- rearranged myeloproliferative neoplasm. Am J Hematol. 2016;91(9):E353.</ref>.

</blockquote>

==Individual Region Genomic Gain / Loss / LOH==

|}

t(5:12)(q32;p13.2), translocation resulting in ETV6-PDGFRB.

</blockquote>

==Gene Mutations (SNV / INDEL)==

Fusion results in the joining of the N-terminal domain of ETV6 to the tyrosine kinase-containing C-terminal of PDGFRB. This leads to oligomerization at the pointed domain, constituently active phosphorylation, and activation of STAT proteins<ref>Chen J, Williams IR, Kutok JL, Duclos N, Anastasiadou E, Masters SC, et al. Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation. Blood. 2004;104(2):535–42.</ref>.

</blockquote>

==Epigenomic Alterations==

|}

PDGFRB encodes a plasma membrane-spanning receptor with five extracellular immunoglobulin-like loops for ligand binding and a split intracellular tyrosine kinase domain. Signal transduction is very similar, with ligand binding inducing dimerization and autophosphorylation of the tyrosine kinase. In addition to its role in embryonic development, PDGFRB mediates chemotactic responses of monocytes, macrophages, and platelets to inflammatory processes. Overexpression has been implicated in solid tumors, such as medulloblastoma and chordoma<ref>Chang, C. C., & Ohgami, R. S. (Eds.). (2018). ''Precision molecular pathology of myeloid neoplasms''. Springer.</ref>.

</blockquote>

==Genetic Diagnostic Testing Methods==