New molecular markers of CML progression

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , ,

V.A. Misyurin1,2, A.V. Misyurin1,2, L.A. Kesayeva1,2, Yu.P. Finashutina1,2, Ye.N. Misyurina2, I.N. Soldatova1,2, A.A. Krutov2, N.A. Lyzhko1,2, T.V. Akhlynina1,2, A.Ye. Lukina3, T.I. Kolosheynova3, N.V. Novitskaya1, Ye.G. Arshanskaya4, Ye.G. Ovsyannikova5, R.A. Golubenko6, V.A. Lapin7, T.I. Pospelova8, V.A. Tumakov9, and A.Yu. Baryshnikov1

1 N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation

2 GeneTechnology Medical Center, Moscow, Russian Federation

3 Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation

4 Moscow Hematological City Center, S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

5 Astrakhan State Medical Academy, Astrakhan, Russian Federation

6 Orel Regional Clinical Hospital, Orel, Russian Federation

7 Hematological Center, Yaroslavl City Clinical Hospital #1, Yaroslavl, Russian Federation

8 Novosibirsk State Medical University, Novosibirsk, Russian Federation

9 Ivanovo Regional Clinical Hospital #1, Ivanovo, Russian Federation

ABSTRACT

In the contrast to Ph’-negative chronic myeloproliferative disorders (cMPD), chronic myelogenous leukemia (CML) is prone to rather early transformation into the later stage disease, known as the acceleration phase (AP) and blast crisis (BC). Myeloproliferative disorders are termed myeloproliferative neoplasms in the WHO classification, 2008. Molecular mechanisms underlying CML progression are unclear and still being studied. Recently, it was shown that progression of some malignancies was associated with activation and hyperexpression of some genes from the cancer-testis (CT) family. In this study, we evaluated the gene expression profile of CT genes (GAGE1, NY-ESO-1, MAGEA1, SCP1, SEMG1, SPANXA1, SSX1 and PRAME) in the blood of patients with initially diagnosed cMPD, as well as in the blood and bone marrow of CML patients in CP, AP and BC. It was found that activation of these eight CT genes expression was strongly correlated with CML progression to AP and BP. These data suggest that at least some of CT genes can be involved in CML evolution towards the terminal phases. Expression of these genes can be used as an early molecular predictor of CML progression to AP and BC.

Keywords: cancer-testis genes, PRAME, gene expression, chronic myelogenous leukemia, chronic myeloproliferative diseases

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