Huiquan Tao1, Xiao Ma2, Guangsong Su1, Jiawei Yin1, Xiaoli Xie1, Chenxi Hu1, Zheng Chen1, Dongming Tan1, Zhongjuan Xu1, Yanwen Zheng1, Hong Liu2, Chao He1, Zhengwei Jenny Mao3, Hongchao Yin4, Zhiwei Wang1, Weirong Chang2, Robert Peter Gale5, Zixing Chen2, Depei Wu2, Bin Yin6. 1. Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Soochow University, Suzhou, Jiangsu province, China. 2. The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology, Suzhou, Jiangsu province, China. 3. Seattle Cancer Center Alliance, University of Washington Medical Center, Seattle, WA, USA. 4. Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China. 5. Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London SW7 2AZ, UK. 6. Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Soochow University, Suzhou, Jiangsu province, China; Thrombosis and Hemostasis Key Lab of the Ministry of Health, Soochow University, Suzhou, Jiangsu province, China; Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu province, China. Electronic address: yinbin@hotmail.com.
Abstract
BACKGROUND: BCL11A encodes a C2H2 type zinc-finger protein. During normal haematopoietic cell differentiation BCL11A expression is down-regulated. Data in mice suggest up-regulation of BCL11A is involved in the pathogenesis of myeloid leukaemias. BCL11A expression in persons with acute myeloid leukaemia (AML) is not systematically studied. OBJECTIVE: Interrogate associations between BCL11A expression at diagnosis and clinical and laboratory valuables and outcomes in newly-diagnosed persons with AML. METHODS: We determined BCL11A mRNA levels in bone marrow and blood mononuclear cells in 292 consecutive newly-diagnosed subjects with AML by reverse transcript and real-time polymerase chain reaction. Data were compared to mRNA levels in bone marrow cells of normals. RESULTS: Subjects with BCL11A transcript levels at diagnosis exceeding the median value of 2.434 (±3.423 SD; 25th-75th inter-quartile range, 1.33-4.29) had higher WBC levels, a greater proportion of bone marrow myeloblasts, were more likely to be FAB M0 subtype, less likely to be FAB M3 subtype, more likely to be in the intermediate cytogenetic risk cohort, less likely to have a complex karyotype and more likely to have DNMT3A(R882) and FLT3-ITD mutations than subjects with transcript levels below the median value. In 89 subjects receiving conventional induction chemotherapy the complete remission rate was 54% (95% confidence interval [CI]; 33, 75%) in the lower BCL11A cohort and 65% (45, 85%; P=0.26) in the higher BCL11A cohort. 3 year survival was 33% (2, 65%) in the lower BCL11A cohort and 15% (0, 39%; P=0.35) in the high BCL11A cohort. CONCLUSION: BCL11A transcript levels at diagnosis was significantly associated with several clinical and laboratory variables. There were also non-significant associations with complete remission rate and survival. These data suggest a possible role for BCL11A expression in AML biology.
BACKGROUND:BCL11A encodes a C2H2 type zinc-finger protein. During normal haematopoietic cell differentiation BCL11A expression is down-regulated. Data in mice suggest up-regulation of BCL11A is involved in the pathogenesis of myeloid leukaemias. BCL11A expression in persons with acute myeloid leukaemia (AML) is not systematically studied. OBJECTIVE: Interrogate associations between BCL11A expression at diagnosis and clinical and laboratory valuables and outcomes in newly-diagnosed persons with AML. METHODS: We determined BCL11A mRNA levels in bone marrow and blood mononuclear cells in 292 consecutive newly-diagnosed subjects with AML by reverse transcript and real-time polymerase chain reaction. Data were compared to mRNA levels in bone marrow cells of normals. RESULTS: Subjects with BCL11A transcript levels at diagnosis exceeding the median value of 2.434 (±3.423 SD; 25th-75th inter-quartile range, 1.33-4.29) had higher WBC levels, a greater proportion of bone marrow myeloblasts, were more likely to be FAB M0 subtype, less likely to be FAB M3 subtype, more likely to be in the intermediate cytogenetic risk cohort, less likely to have a complex karyotype and more likely to have DNMT3A(R882) and FLT3-ITD mutations than subjects with transcript levels below the median value. In 89 subjects receiving conventional induction chemotherapy the complete remission rate was 54% (95% confidence interval [CI]; 33, 75%) in the lower BCL11A cohort and 65% (45, 85%; P=0.26) in the higher BCL11A cohort. 3 year survival was 33% (2, 65%) in the lower BCL11A cohort and 15% (0, 39%; P=0.35) in the high BCL11A cohort. CONCLUSION:BCL11A transcript levels at diagnosis was significantly associated with several clinical and laboratory variables. There were also non-significant associations with complete remission rate and survival. These data suggest a possible role for BCL11A expression in AML biology.
Authors: Kyren A Lazarus; Fazal Hadi; Elisabetta Zambon; Karsten Bach; Maria-Francesca Santolla; Julie K Watson; Lucia L Correia; Madhumita Das; Rosemary Ugur; Sara Pensa; Lukas Becker; Lia S Campos; Graham Ladds; Pentao Liu; Gerard I Evan; Frank M McCaughan; John Le Quesne; Joo-Hyeon Lee; Dinis Calado; Walid T Khaled Journal: Nat Commun Date: 2018-08-20 Impact factor: 14.919
Authors: Denise Anderson; Patrycja Skut; Anastasia M Hughes; Emanuela Ferrari; Jennifer Tickner; Jiake Xu; Benjamin H Mullin; Dave Tang; Sébastien Malinge; Ursula R Kees; Rishi S Kotecha; Timo Lassmann; Laurence C Cheung Journal: Sci Rep Date: 2020-11-05 Impact factor: 4.379