RET fusion genes are associated with chronic myelomonocytic leukemia and enhance monocytic differentiation

被引：81

作者：

Ballerini, P. ^{[2
]}

Struski, S.

Cresson, C. ^{[3
]}

Prade, N.

Toujani, S. ^{[4
]}

Deswarte, C. ^{[2
]}

Dobbelstein, S.

Petit, A. ^{[2
]}

Lapillonne, H. ^{[2
]}

Gautier, E-F ^{[3
]}

Demur, C.

Lippert, E. ^{[5
,6
]}

Pages, P. ^{[2
]}

Mansat-De Mas, V. ^{[3
,7
,8
]}

Donadieu, J. ^{[2
]}

Huguet, F.

Dastugue, N.

Broccardo, C. ^{[3
]}

Perot, C. ^{[4
]}

Delabesse, E. ^{[1
,3
,7
,8
]}

机构：

[1] Hop Purpan, Dept Hematol, Hematol Lab, F-31059 Toulouse 9, France

[2] Hop Trousseau, APHP, Dept Hematol, F-75571 Paris, France

[3] Ctr Rech Canc Toulouse, Inst Natl Sante & Rech Med U1037, Toulouse, France

[4] Hop St Antoine, APHP, Dept Cytogenet, F-75571 Paris, France

[5] CHU Bordeaux, Dept Hematol, Bordeaux, France

[6] Univ Victor Segalen, INSERM U1035, Bordeaux, France

[7] CHU Toulouse, Toulouse, France

[8] Univ Toulouse 2, Toulouse, France

来源：

LEUKEMIA | 2012年 / 26卷 / 11期

关键词：

tyrosine kinase; sorafenib; CMML; RECEPTOR TYROSINE KINASE; PAPILLARY THYROID-CARCINOMA; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELLS; BCR-ABL; MUTATIONS; ACTIVATION; RAS; IDENTIFICATION; TRANSFORMATION;

D O I：

10.1038/leu.2012.109

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from chimaeric fusion genes or point mutations such as BCR-ABL1 or JAK2 V617F. We report here the cloning and functional characterization of two novel fusion genes BCR-RET and FGFR1OP-RET in chronic myelomonocytic leukemia (CMML) cases generated by two balanced translocations t(10; 22)(q11;q11) and t(6;10)(q27;q11), respectively. The two RET fusion genes leading to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. The RET fusion genes seem to constitutively mimic the same signaling pathway as RAS mutations frequently involved in CMML. One patient was treated with Sorafenib, a specific inhibitor of the RET TK function, and demonstrated cytological and clinical remissions.

引用

页码：2384 / 2389

页数：6

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