Fetal hemoglobin in sickle cell anemia

被引:353
作者
Akinsheye, Idowu [1 ]
Alsultan, Abdulrahman [2 ]
Solovieff, Nadia [3 ]
Duyen Ngo [1 ]
Baldwin, Clinton T. [1 ]
Sebastiani, Paola [3 ]
Chui, David H. K. [1 ]
Steinberg, Martin H. [1 ]
机构
[1] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA
[2] King Saud Univ, Coll Med, Dept Pediat, Riyadh 11461, Saudi Arabia
[3] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA
基金
美国国家卫生研究院;
关键词
QUANTITATIVE TRAIT LOCUS; GLOBIN GENE-EXPRESSION; GENOME-WIDE ASSOCIATION; BETA-THALASSEMIA; HB-F; CHROMOSOME; 8Q; SAUDI ARABS; LEG ULCERS; G-GAMMA; HYDROXYUREA;
D O I
10.1182/blood-2011-03-325258
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers. (Blood. 2011;118(1):19-27)
引用
收藏
页码:19 / 27
页数:9
相关论文
共 95 条
[61]  
PERRINE RP, 1972, LANCET, V2, P1163
[62]   HYDROXYUREA ENHANCES FETAL HEMOGLOBIN PRODUCTION IN SICKLE-CELL-ANEMIA [J].
PLATT, OS ;
ORKIN, SH ;
DOVER, G ;
BEARDSLEY, GP ;
MILLER, B ;
NATHAN, DG .
JOURNAL OF CLINICAL INVESTIGATION, 1984, 74 (02) :652-656
[63]   MORTALITY IN SICKLE-CELL DISEASE - LIFE EXPECTANCY AND RISK-FACTORS FOR EARLY DEATH [J].
PLATT, OS ;
BRAMBILLA, DJ ;
ROSSE, WF ;
MILNER, PF ;
CASTRO, O ;
STEINBERG, MH ;
KLUG, PP .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 330 (23) :1639-1644
[64]   IS THERE A THRESHOLD LEVEL OF FETAL HEMOGLOBIN THAT AMELIORATES MORBIDITY IN SICKLE-CELL-ANEMIA [J].
POWARS, DR ;
WEISS, JN ;
CHAN, LS ;
SCHROEDER, WA .
BLOOD, 1984, 63 (04) :921-926
[65]  
Rodgers GP, 2001, DISORDERS HEMOGLOBIN, P1028
[66]   MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13 [J].
Sankaran, Vijay G. ;
Menne, Tobias F. ;
Scepanovic, Danilo ;
Vergilio, Jo-Anne ;
Ji, Peng ;
Kim, Jinkuk ;
Thiru, Prathapan ;
Orkin, Stuart H. ;
Lander, Eric S. ;
Lodish, Harvey F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (04) :1519-1524
[67]   Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A [J].
Sankaran, Vijay G. ;
Menne, Tobias F. ;
Xu, Jian ;
Akie, Thomas E. ;
Lettre, Guillaume ;
Van Handel, Ben ;
Mikkola, Hanna K. A. ;
Hirschhorn, Joel N. ;
Cantor, Alan B. ;
Orkin, Stuart H. .
SCIENCE, 2008, 322 (5909) :1839-1842
[68]   Effects of 5-aza-2′-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease [J].
Saunthararajah, Y ;
Hillery, CA ;
Lavelle, D ;
Molokie, R ;
Dorn, L ;
Bressler, L ;
Gavazova, S ;
Chen, YH ;
Hoffman, R ;
DeSimone, J .
BLOOD, 2003, 102 (12) :3865-3870
[69]   Fetal hemoglobin in sickle cell anemia: Bayesian modeling of genetic associations [J].
Sebastiani, Paola ;
Wang, Ling ;
Nolan, Vikki G. ;
Melista, Efthymia ;
Ma, Qianli ;
Baldwin, Clinton T. ;
Steinberg, Martin H. .
AMERICAN JOURNAL OF HEMATOLOGY, 2008, 83 (03) :189-195
[70]   BCL11A is a major HbF quantitative trait locus in three different populations with β-hemoglobinopathies [J].
Sedgewick, Amanda E. ;
Timofeev, Nadia ;
Sebastiani, Paola ;
So, Jason C. C. ;
Ma, Edmond S. K. ;
Chan, Li Chong ;
Fucharoen, Goonnapa ;
Fucharoen, Supan ;
Barbosa, Cynara G. ;
Vardarajan, Badri N. ;
Farrer, Lindsay A. ;
Baldwin, Clinton T. ;
Steinberg, Martin H. ;
Chui, David H. K. .
BLOOD CELLS MOLECULES AND DISEASES, 2008, 41 (03) :255-258