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myeloproliferative disorder

Etiology: - acquired, clonal mutations of the pluripotent hematopoietic stem cell Pathology: 1) expanded proliferation of the abnormal clone at the expense of normal cells - deregulated production of leukocytes, eosinophils, erythrocytes or platelets - myeloid hyperplasia 2) affected stem cells tend to proliferate in culture without addition of growth factors 3) increased risk of thrombotic & hemorrhagic complications 4) splenomegaly is common 5) transformation into therapy-resistant acute leukemia is common 6) activation of mast cells & CD3+ T-cells to overproduce IL-31 (pruritic) & impair release prostaglandin D2 (pruritus inhibitor) [2] 7) T-cell or B-cell lymphoblastic lymphoma 8) in general it progresses to acute myeloid leukemia Genetics: - chromosomal translocation t(6;8)(q27;p11) with FGFR1OP with FGFR1 may be a cause of stem cell myeloproliferative disorder - chromosomal translocation t(1;5)(q23;q33) involving PDE4DIP with PDGFRB may be the cause of a myeloproliferative disorder associated with eosinophilia translocation forms a PDE4DIP- PDGFRB fusion protein - chromosomal insertion ins(12;8)(p11;p11p22) involving FGFR1OP2 with FGFR1 may be a cause of stem cell myeloproliferative disorder, fusion protein FGFR1OP2-FGFR1 may exhibit constitutive kinase activity & be responsible for the transforming activity - chromosomal translocation t(8;9)(p12;q33) involving CEP110 with FGFR1 may be a cause of stem cell myeloproliferative disorder - other implicated genes: EVI2A, EVI2B Clinical manifestations: - pruritus may be continuous or induced by a hot shower [2] Laboratory: 1) complete blood count (CBC) - eosinophilia 2) bone marrow biopsy 3) erythroid colony assay may allow early diagnosis of myelproliferative disorder 4) JAK2 V617F mutations in initial workup of all patients [11] 5) left-shifted leukocytosis &/or thrombocytosis with basophilia - fluorescence in situ hybridization (FISH) or - multiplex RT-PCR on peripheral blood for BCR/ABL mRNA to rule out chronic myeloid leukemia (CML) [11] 6) after confirmatinf diagnosis of myeloproliferative neoplasm - multigene next generation sequencing panel including - JAK2, CALR, & MPL [11] 7) see ARUP consult [3] Management: 1) see specific etiology 2) anticoagulation & hydroxyurea to lower platelet counts in patients with thrombosis 3) pruritus may respond to SSRI; antihistaminics & NSAIDs are usually ineffective [2]

Related

myelodysplastic syndrome (MDS)

Specific

chronic myeloproliferative disorder eosinophilic leukemia leukemoid reaction myelofibrosis myeloid leukemia myeloid metaplasia myeloid sarcoma (extramedullary myeloid tumor, granulocytic sarcoma, chloroma) stem cell leukemia lymphoma syndrome (SCLL)

General

immunoproliferative disorder myeloid disorder

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  2. Ishii T et al Pivotal role of mast cells in pruritogenesis in patients with myeloproliferative disorders. Blood 2009 Jun 4; 113:5942. PMID: 19196660
  3. ARUP Consult: Myeloproliferative Neoplasms - MPN The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/myeloproliferative-neoplasms - ARUP consult: Myeloid Malignancies Mutation Panel by Next Generation Sequencing https://arupconsult.com/ati/myeloid-malignancies-mutation-panel-next-generation-sequencing
  4. Tefferi A, Skoda R, Vardiman JW. Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. Nat Rev Clin Oncol. 2009 Nov;6(11):627-37. PMID: 19806146
  5. Vardiman JW, Thiele J, Arber DA et al The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. PMID: 19357394
  6. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia. 2008 Jan;22(1):14-22. Epub 2007 Sep 20 PMID: 17882280
  7. Spivak JL Myeloproliferative Neoplasms. N Engl J Med 2017; 376:2168-2181. June 1, 2017 PMID: 28564565 http://www.nejm.org/doi/full/10.1056/NEJMra1406186
  8. Mesa RA, Jamieson C, Bhatia R, et al. NCCN guidelines insights: myeloproliferative neoplasms, version 2.2018. J Natl Compr Canc Netw. 2017 Oct;15(10):1193-207 PMID: 28982745
  9. Nangalia J, Massie CE, Baxter EJ et al Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013 Dec 19;369(25):2391-2405. Epub 2013 Dec 10. PMID: 24325359 Free PMC Article
  10. Arber DA, Orazi A, Hasserjian R et al The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. Review. PMID: 27069254 Free Article
  11. National Comprehensive Cancer Network Myeloproliferative Neoplasms Clinical Practice Guidelines (NCCN, 2022) Medscape. September 30, 2022 https://reference.medscape.com/viewarticle/978759
  12. Myeloproliferative Disorders http://www.cancer.gov/cancerinfo/types/myeloproliferative - Chronic Myeloproliferative Disorders (PDQ): Treatment http://www.nci.nih.gov/cancertopics/pdq/treatment/myeloproliferative/HealthProfessional