Dual targeting of MCL1 and NOXA as effective strategy for treatment of mantle cell lymphoma

被引：13

作者：

Hoering, Elisabeth ^{[1
,2
,3
,4
]}

Montraveta, Arnau ^{[4
]}

Heine, Simon ^{[1
,2
]}

Kleih, Markus ^{[1
,2
]}

Schaaf, Lea ^{[1
,2
]}

Voehringer, Matthias C. ^{[3
]}

Esteve-Arenys, Anna ^{[4
]}

Roue, Gael ^{[4
]}

Colomer, Dolors ^{[4
]}

Campo, Elias ^{[4
]}

Ott, German ^{[5
]}

Aulitzky, Walter E. ^{[3
]}

van der Kuip, Heiko ^{[1
,2
]}

机构：

[1] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, D-70376 Stuttgart, Germany

[2] Univ Tubingen, Tubingen, Germany

[3] Robert Bosch Krankenhaus, Dept Haematol & Oncol, Stuttgart, Germany

[4] Univ Barcelona, IDIBAPS, Haematopathol Unit, Hosp Clin, Barcelona, Spain

[5] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2017年 / 177卷 / 04期

关键词：

mantle cell lymphoma; NOXA; MCL1; Dinaciclib; FASNi; DEPENDENT KINASE INHIBITOR; DINACICLIB; BORTEZOMIB; RESPONSES; LEUKEMIA;

D O I：

10.1111/bjh.14571

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Imbalances in the composition of BCL2 family proteins contribute to tumourigenesis and therapy resistance of mantle cell lymphoma (MCL), making these proteins attractive therapy targets. We studied the efficiency of dual targeting the NOXA/MCL1 axis by combining fatty acid synthase inhibitors (NOXA stabilization) with the CDK inhibitor Dinaciclib (MCL1 reduction). This combination synergistically induced apoptosis in cell lines and primary MCL cells and led to almost complete inhibition of tumour progression in a mouse model. Apoptosis was NOXA-dependent and correlated with the NOXA/MCL1 ratio, highlighting the importance of the NOXA/MCL1 balance for effective cell death induction in MCL.

引用

页码：557 / 561

页数：5

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