HAEM5:Myeloid/lymphoid neoplasm with JAK2 rearrangement: Difference between revisions

Patients typically present with features of a myeloproliferative disorder or MDS/MPN and most have eosinophilia and/or bone marrow  fibrosis<ref name=":2" /><ref name=":1">{{Cite journal|last=Hoeller|first=Sylvia|last2=Walz|first2=Christoph|last3=Reiter|first3=Andreas|last4=Dirnhofer|first4=Stephan|last5=Tzankov|first5=Alexandar|date=2011|title=PCM1–JAK2-fusion: a potential treatment target in myelodysplastic–myeloproliferative and other hemato-lymphoid neoplasms|url=http://www.tandfonline.com/doi/full/10.1517/14728222.2011.538683|journal=Expert Opinion on Therapeutic Targets|language=en|volume=15|issue=1|pages=53–62|doi=10.1517/14728222.2011.538683|issn=1472-8222}}</ref>. Patients in chronic phase tend to progress to AML quickly; some present with de novo acute leukemia, either myeloid or lymphoid<ref name=":1" /><ref name=":2" />

In general, patients with this disorder have weakness/fatigue (~26%), cough (~24%), myaligias/angioedema (~14%), rash or fever (~12%) and rhinitis (~10%)<ref>{{Cite journal|last=Gotlib|first=Jason|date=2017|title=World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management|url=http://doi.wiley.com/10.1002/ajh.24880|journal=American Journal of Hematology|language=en|volume=92|issue=11|pages=1243–1259|doi=10.1002/ajh.24880}}</ref> ; lymphadenopathy and splenomegaly are common<ref name=":2" />  

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==Sites of Involvement==

IHC can be used to characterize acute myeloid transformation and myeloblasts express dim CD45, dim CD34, dim CD117, HLA-DR, dim CD33, and dim CD13<ref name=":0" />. In addition, For the cases with lymphoid components, IHC can assist with assessment and show dim CD19 and dim CD10, consistent with lymphoblast lineage<ref name=":0" /><ref name=":2" />.

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==Chromosomal Rearrangements (Gene Fusions)==

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

Most patients present with MPN with variable degrees of eosinophilia in blood and/or bone marrow, frequent marrow fibrosis, and large aggregates of immature erythroid precursors, and clinically exhibit hepatosplenomegagly and lymphadenopathy<ref name=":2" />. However, diagnosis may be difficult in cases without obvious eosinophilia.  

Due to the variations in presentation, the prognosis is mainly dependent on the phase at presentation, but generally tends to have an aggressive course¹. There currently are no approved therapies for ''PCM1/JAK2''-mediated myeloid/lymphoid neoplasm with eosinophilia; however, ''JAK2'' inhibitors have been approved for other hematopoietic neoplasms with constitutively activated ''JAK2'' kinases.²

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

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There are no known recurrent genomic loss/gain or LOH pattern associated with entity.

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==Characteristic Chromosomal Patterns==

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There are no known secondary chromosomal changes and no pattern of other chromosome aberrations.   

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==Gene Mutations (SNV / INDEL)==

Given the rarity of the entity, there are no known recurrent aberrations. For the largest series studied, most cases were negative for mutations. However, some cases showed variants in genes associated with myeloid malignancies (ASXL1, RUNX1, SRSF2, TET2, BCOR) and one patient with B-ALL transformation showed variants in ETV6 and TP53<ref name=":2" />

===Other Mutations===

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==Epigenomic Alterations==

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''PCM1'' (pericentriolar material 1) is a protein present in cytoplasmic granules and can be found in association with the centrosome. ''PCM1'' is indirectly responsible for microtubule anchoring, which is necessary for a variety of cellular functions, including intracellular transport and cell division. The gene is located at band 8p22 and includes 41 exons.⁵

The PCM1-JAK2 fusion product retains the coiled-coil domains of ''PCM1'' and the activating tyrosine kinase domain of ''JAK2''. Thus PCM1-JAK2 fusion produces an aberrant tyrosine kinase that results in constitutive activation of the JAK2–STAT pathway<ref name=":1" />

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==Genetic Diagnostic Testing Methods==