A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease

Pule, Gift D.; Mowla, Shaheen; Novitzky, Nicolás; Wiysonge, Charles Shey; Wonkam, Ambroise

doi:10.1586/17474086.2015.1078235

Cited by 75 publications

(66 citation statements)

References 136 publications

(131 reference statements)

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“…Further utility of the HDCA will derive from comparative analyses of adult and fetal cell maps to understand development and ageing. These will additionally define fetal analogues of adult transcripts, which could be exploited for therapy, as in the induction of fetal haemoglobin by hydroxyurea in the treatment of sickle cell disease (Pule et al, 2015).…”

Section: The Big Picturementioning

confidence: 99%

Mapping human development at single-cell resolution

et al. 2018

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Human development is regulated by spatiotemporally restricted molecular programmes and is pertinent to many areas of basic biology and human medicine, such as stem cell biology, reproductive medicine and childhood cancer. Mapping human development has presented significant technological, logistical and ethical challenges. The availability of established human developmental biorepositories and the advent of cutting-edge single-cell technologies provide new opportunities to study human development. Here, we present a working framework for the establishment of a human developmental cell atlas exploiting single-cell genomics and spatial analysis. We discuss how the development atlas will benefit the scientific and clinical communities to advance our understanding of basic biology, health and disease.

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Section: The Big Picturementioning

confidence: 99%

Mapping human development at single-cell resolution

et al. 2018

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“…There were several barriers to HU treatment, including the financial implications of taking time off work to attend the clinic and receive it (maximum one month's supply), and misconceptions about the treatment and its possible carcinogenic effects, as well as potential impotence in male patients. [39] Most patients who fail to comply with clinic appointments do so simply because they feel better and therefore see no need to go to the hospital.…”

Section: Researchmentioning

confidence: 99%

Burden, genotype and phenotype profiles of adult patients with sickle cell disease in Cape Town, South Africa

et al. 2017

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Background. An exponential increase in the number of sickle cell disease (SCD) patients in paediatric services in Cape Town, South Africa, has been reported. The trend in adult/adolescent services has not been investigated. Objectives. To evaluate epidemiological trends of SCD and the profile of patients affected by SCD attending the Haematology Clinic at Groote Schuur Hospital (GSH), Cape Town. Methods. (i)A retrospective review of the number of SCD patients over the past 20 years; (ii) a cross-sectional analysis of clinical and haematological characteristics of SCD patients; and (iii) molecular analysis of the haemoglobin S mutation, the haplotype in the β-globinlike genes cluster, the 3.7 kb α-thalassaemia gene deletion and 19 selected single-nucleotide polymorphisms (SNPs) associated with fetal haemoglobin (HbF) levels. Results. From 1995 to 2016, 81 adolescent/adult patients with SCD were registered, mostly originating from other African countries (n=61, 75.3%). There was an increase of over 200% in new cases (n=47) during the last quarter of the two decades investigated. Data from 34 of 58 regular attendees (58.6%) were analysed. The mean age of the patients was 26.1 years (standard deviation (SD) 9.8), and 70.6% were male. With the exception of four patients with sickle/β-thalassaemia, all the patients had SCD (haemoglobin SS). The co-inheritance of a single 3.7 kb α-globin deletion was found in 42.3% of cases (n=11). The Bantu haplotype was the most observed (65.4% of chromosomes). Most HbF-promoting SNPs were not associated with variable levels of haematological indices. Conclusions.There is an increasing burden of adult SCD patients at GSH. National health and academic institutions need to adapt policies and healthcare professional training accordingly. S Afr Med RESEARCH Methods Ethical approvalThe study was performed in accordance with the Declaration of Helsinki and with the approval of the Faculty of Health Sciences Human Research Ethics Committee, University of Cape Town (HREC ref. no. 132/2010). Informed and written consent was obtained from adult participants (≥18 years), and for one patient aged 15 years informed consent was obtained from the guardian with assent from the participant. PatientsThe Haematology Clinic runs weekly every Wednesday. Most patients are seen at least once a month, and clinically stable patients every 3 months, with the exception of crisis-related hospitalisation.A retrospective review of the number of SCD patients attending the clinic over the past 20 years and a cross-sectional analysis of patients who regularly attend the clinic were performed. Clinical events and haematological indices were retrospectively collected from hospital records. The haematological measures were those reported at the first visit to the hospital. Molecular methods DNA extractionDNA was isolated from the peripheral blood using the AllPrep DNA/RNA/miRNA universal kit (Qiagen, USA) according to the manufacturer's instructions. GenotypingHbS mutation and β-globin haplotypes Polymerase chain reac...

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“…Fetal hemoglobin (HbF) has emerged as a central disease modifier and genetic variants at three principal loci, BCL11A, HBS1L-MYB, and HBB cluster, which account for 10-20% of HbF variation among SCD patients in USA, Brazil, and the United Kingdom (Lettre et al, 2008;Thein and Menzel, 2009). These studies have been replicated in patients living with SCD in Tanzania and Cameroon (Makani et al, 2011;Mtatiro et al, 2014;Pule et al, 2015;Wonkam et al, 2014a). Interestingly, the expression of these modifiers is amenable to therapeutic manipulation (Bukar et al, 2013;Canver et al, 2015;Xu et al, 2011), leading to new hope for treatment routes for SCD (Orkin, 2016).…”

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confidence: 92%

“…As a consequence, up to 90% of infants with SCD in SSA are believed to die by the age of 5 years (Grosse et al, 2011;Makani et al, 2013). While there have been recent efforts in selected African countries to implement newborn screening (McGann et al, 2013;Rahimy et al, 2009;Tshilolo et al, 2009;Tubman et al, 2016), to use hydroxyurea (HU) more frequently (Makubi et al, 2012;Olabode and Shokunbi, 2006;Ware, 2013), and to initiate genetic studies (Cox et al, 2014;Mmbando et al, 2015;Mtatiro et al, 2014;Pule et al, 2015;Rumaney et al, 2014;Wonkam et al, 2014aWonkam et al, , 2014bWonkam et al, , 2014c, there is still a lack of integration and coordination of these emerging research efforts.…”

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confidence: 99%

An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine

Mnika

Pule

Dandara

et al. 2016

OMICS: A Journal of Integrative Biology

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Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a stateof-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids. The literature search used the following keywords: SCD, pharmacogenomics, pharmacogenetics, pain, antalgics, opioids, morphine, and HU. The literature was scanned until March 2016, with specific inclusion of targeted landmark and background articles on SCD. Surprisingly, our review identified only a limited number of studies that addressed the genetic/genomic basis of variable responses to pain (e.g., variants in OPRM1, HMOX-1, GCH1, VEGFA COMT genes), and pharmacogenomics of antalgics and opioids (e.g., variants in OPRM1, STAT6, ABCB1, and COMT genes) in SCD. There has been greater progress made toward identifying the key genomic variants, mainly in BCL11A, HBS1L-MYB, or SAR1, which contribute to response to HU treatment. However, the complete picture on pharmacogenomic determinants of the above therapeutic phenotypes remains elusive. Strikingly, no study has been conducted in sub-Saharan Africa where majority of the patients with SCD live. This alerts the broader global life sciences community toward the existing disparities in optimal and ethical targeting of research and innovation investments for SCD specifically and precision medicine and pharmacology research broadly.

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A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease

Cited by 75 publications

References 136 publications

Mapping human development at single-cell resolution

Mapping human development at single-cell resolution

Burden, genotype and phenotype profiles of adult patients with sickle cell disease in Cape Town, South Africa

An Expert Review of Pharmacogenomics of Sickle Cell Disease Therapeutics: Not Yet Ready for Global Precision Medicine

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