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Clonal analysis of erythroid progenitors suggests that pegylated interferon α-2a treatment targets JAK2V617F clones without affecting TET2 mutant cells

Leukemia volume 24, pages 1519–1523 (2010)Cite this article

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Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by an excess of production of red blood cells driven by mutations in the Janus kinase 2 (JAK2) gene.1 The most frequent mutation underlying PV is the JAK2V617F mutation, found in approximately 95% of cases. Rare JAK2V617F-negative cases have other mutations in JAK2. Recently, TET2 mutations have been found in approximately 15% of PV cases,2, 3 but a clear clinical or prognostic effect of those mutations has not been evidenced.3 These additional molecular abnormalities can be detected in the founder clone of the disease, but may also be found in a JAK2V617F-independent clone, or as secondary defects that could participate to the progression of the disease to a myelofibrotic or a blast phase.4, 5

Interferon α-2a (IFNa) treatment has been shown to induce complete hematologic response, cytogenetic remission or reversion from monoclonal to polyclonal hematopoiesis in studies on few occasional PV patients. In a phase 2 trial of peg-IFNa, we observed a substantial decrease in JAK2V617F allele burden in peripheral blood granulocytes from 29 patients treated with IFNa alone.6 In 7 out of 29 patients (24%), JAK2 mutant alleles even became undetectable using an allele-specific PCR assay with a 1% sensitivity (baseline mutant JAK2 burden and time to complete molecular remission (CMR) are reported in Table 1). With these seven cases of CMRs, we were able to identify, by JAK2V617F monitoring, the first homogeneous cohort of patients with measurable reduction of the PV clone. The study of this cohort may allow answering whether such CMR are associated with elimination of the PV clone.

Table 1 SPC and MC assays in JAK2V617F CMR patients
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Acknowledgements

This work received funding from the MPD foundation, the Association Laurette Fugain, the Fondation de france and the Institut National du Cancer. This work was supported by grants from the Ligue Nationale Contre le Cancer (équipe labelisée 2009). This letter is dedicated to Sabrina Dupont whose work greatly contributed to the discovery of TET2 mutations in MPNs.

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Authors and Affiliations

  1. Centre d’Investigations Cliniques—CIC 9504, Assistance Publique -Hôpitaux de Paris, Hôpital Saint-Louis,

    J-J Kiladjian

  2. Université Paris 7, Paris, France

    J-J Kiladjian

  3. INSERM U1009, Institut Gustave Roussy, Villejuif, France

    A Massé, H Mokrani, J-P le Couédic, C Almire, E Pronier, N Casadevall, W Vainchenker & F Delhommeau

  4. Unité de Biologie Cellulaire, Assistance Publique—Hôpitaux de Paris, Hôpital Saint-Louis, Paris, France

    B Cassinat & C Chomienne

  5. Laboratoire d’Hématologie et d’Immunologie, Assistance Publique—Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France

    I Teyssandier, N Casadevall & F Delhommeau

  6. Service des Maladies du Sang, CHRU Huriez, Lille, France

    N Cambier

  7. Université Paris 6 Pierre et Marie Curie, Paris, France

    N Casadevall & F Delhommeau

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for the French Intergroup of Myeloproliferative Neoplasms (FIM)

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Correspondence to F Delhommeau.

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Kiladjian, JJ., Massé, A., Cassinat, B. et al. Clonal analysis of erythroid progenitors suggests that pegylated interferon α-2a treatment targets JAK2V617F clones without affecting TET2 mutant cells. Leukemia 24, 1519–1523 (2010). https://doi.org/10.1038/leu.2010.120

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