NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells

被引：22

作者：

Di Ianni, Mauro ^{[1
,2
]}

Baldoni, Stefano ^{[3
]}

Del Papa, Beatrice ^{[4
]}

Aureli, Patrizia ^{[4
]}

Dorillo, Erica ^{[4
]}

De Falco, Filomena ^{[4
]}

Albi, Elisa ^{[4
]}

Varasano, Emanuela ^{[4
]}

Di Tommaso, Ambra ^{[3
]}

Giancola, Raffaella ^{[2
]}

Accorsi, Patrizia ^{[2
]}

Rotta, Gianluca ^{[5
]}

Rompietti, Chiara ^{[4
]}

Silva Barcelos, Estevao Carlos ^{[4
,6
]}

Campese, Antonio Francesco ^{[7
]}

Di Bartolomeo, Paolo ^{[2
]}

Screpanti, Isabella ^{[7
]}

Rosati, Emanuela ^{[8
]}

Falzetti, Franca ^{[4
]}

Sportoletti, Paolo ^{[4
]}

机构：

[1] Univ G dAnnunzio, Dept Med & Aging Sci, Chieti, Italy

[2] Osped Civile, Dept Hematol Transfus Med & Biotechnol, Pescara, Italy

[3] Univ LAquila, Dept Life Hlth & Environm Sci, Hematol Sect, Laquila, Italy

[4] Univ Perugia, CREO, Inst Hematol, Perugia, Italy

[5] BD Biosci, San Jose, Italy

[6] Univ Fed Espirito Santo, Vitoria, Spain

[7] Sapienza Univ Rome, Dept Mol Med, Rome, Italy

[8] Univ Perugia, Dept Expt Med, Biosci & Med Embriol Sect, Perugia, Italy

来源：

FRONTIERS IN ONCOLOGY | 2018年 / 8卷

关键词：

notch signaling; chronic lymphocytic leukemia; hematopoietic stem cells; NOTCH1; mutation; CD34+ cells; PEST DOMAIN MUTATION; B-CLL; GENETIC LESION; SURVIVAL; EXPRESSION; CANCER;

D O I：

10.3389/fonc.2018.00105

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH/-mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overex-pression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

引用

页数：7

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