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Screening of JAK2 V617F mutation in multiple myeloma

Leukemia volume 20, pages 1912–1913 (2006)Cite this article

Janus tyrosine kinase (JAK) tyrosine kinases are important mediators of cellular signals between cytokines, receptors and effector proteins. They have seven structural domains ‘JAK homology regions’. (JH1–JH7), in particular JH1 and JH2: JH1 has kinase activity, whereas JH2 has a negative-regulatory function on JH1. Recently, a somatic mutation in exon 12 of JAK2 has been described in myeloproliferative diseases: Philadelphia chromosome negative as polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF),1 and more recently this mutation has also been investigated in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), atypical chronic myeloid leukemia (aCML) (BCR-ABL negative), acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL).2, 3 This point mutation results in a substitution of valine for phenylalanine at position 617 (V617F) in the JH2 domain and leads to constitutive tyrosine phosphorylation and cytokine hypersensitivity. Neoplastic cells can be heterozygous for the mutation or hemizygous if they have loss of heterozygosity of 9p chromosome, where JAK2 is located.

JAK2 V617F mutation was identified in 81% (range, 65–97%) of patients with PV, 39% (23–57%) with ET and 43% (35–50%) with idiopatic myelofibrosis (IMF). It was detected, also, in a subset of CMML/aCML, and MDS but not in B-ALL, T-ALL or CLL.2, 3

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References

  1. Baxter EJ, Scott LM, Campbell PJ, East C, Fourclas N, Swanton S, et al., Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054–1061.

    Article  CAS  PubMed  Google Scholar 

  2. Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E et al. The JAK2 activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukaemia, but not in acute lymphoblastic leukaemia or chronic lymphocytic leukaemia. Blood 2005; 106: 3377–3379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sulong S, Case M, Minto L, Wilkins B, Hall A, Irving J . The V617F mutation in JAK2 is not found in childhood acute lymphoblastic leukemia. BrJ Haematol 2005; 130: 964–972.

    Article  Google Scholar 

  4. Melzner I, Weniger MA, Menz CK, Moller P . Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia 2006; 20: 157–158.

    Article  CAS  PubMed  Google Scholar 

  5. Scott LM, Campbell PJ, Baxter EJ, Todd T, Stephens P, Edkins S et al. The V617F JAK2 mutation is uncommon in cancers and myeloid malignancies other than the classic myeloproliferative disorders. Blood 2005; 106: 2920–2921.

    Article  CAS  PubMed  Google Scholar 

  6. De Vos J, Jourdan M, Tarte K, Jasmin C, Klein B . JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription (STAT) pathways and induces apoptosis in myeloma cells. Br J Haematol 2000; 109: 823–828.

    Article  CAS  PubMed  Google Scholar 

  7. Abroun S, Ishikawa H, Tsuyama N, Liu S, Otsuyama KM, Zheng X et al. Receptor synergy of interleukin-6 (IL-6) and insulin-like growth factor-1 in myeloma cells that highly express IL-6 receptor alpha. Blood 2004; 103: 2291–2298.

    Article  CAS  PubMed  Google Scholar 

  8. Bergsagel PL, Masellis S, Szczepek A, Mant MJ, Belch AR, Pilarski LM . In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56 and monotypic immunoglobulin light chain. Blood 1995; 85: 436–447.

    CAS  PubMed  Google Scholar 

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  1. Institute of Hematology, Catholic University, Rome, Italy

    A Fiorini, G Farina, G Reddiconto, M Palladino, E Rossi, T Za, L Laurenti, S Giammarco, P Chiusolo, G Leone & S Sica

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  1. A Fiorini
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  2. G Farina
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Fiorini, A., Farina, G., Reddiconto, G. et al. Screening of JAK2 V617F mutation in multiple myeloma. Leukemia 20, 1912–1913 (2006). https://doi.org/10.1038/sj.leu.2404332

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