Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

Musallam, Khaled M.; Taher, Alì; Cappellini, Maria Domenica; Sankaran, Vijay G.

doi:10.1182/blood-2012-10-408021

Cited by 176 publications

(145 citation statements)

References 136 publications

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“…Another class of compounds that might also benefit b-thalassemia are fetal hemoglobin inducers; these will not be discussed in this manuscript but were recently summarized in several excellent reviews. 37,129,130 …”

Section: Th3/+mentioning

confidence: 99%

“…38 For this reason, drugs that could increase synthesis of HbF are being actively investigated, as reviewed elsewhere. 38,129,130 The transcriptional factor BCL11A has been recognized to be one of most important factors in controlling the switch from HbF to HbA. After birth, as the level of BCL11A increases, the level of HbF decreases, while that of HbA increases.…”

Section: Genome Editingmentioning

confidence: 99%

“…126,127 As mentioned previously, both decreased apoptotic rate and maturation of early erythroid precursors leads to exacerbation of IE, splenomegaly, and increased iron absorption. 117,128,129 Furthermore, these compounds also target the aberrant metabolism that leads to premature osteoporosis in this disorder, improving bone structure in these mice. Clinical trials with these agents are underway, showing amelioration of the anemia in NTDT patients and a potential reduction of the transfusion regimen in patients affected by b-thalassemia major.…”

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confidence: 99%

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-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

2015

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b-thalassemias are monogenic disorders characterized by defective synthesis of the b-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the b-globin gene or its regulatory elements have been associated with b-thalassemias. Due to the complexity of the regulation of the b-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of b-globin and abnormal erythropoiesis, as well as current and novel therapies. ABSTRACTThe complex phenotype of b-thalassemias b-thalassemias are monogenic disorders characterized by reduced or no synthesis of the b-globin chain, one of the major components of adult hemoglobin (HbA). Several hundred mutations in the b-globin gene or regulatory elements have been associated with b-thalassemias.

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Section: Th3/+mentioning

confidence: 99%

Section: Genome Editingmentioning

confidence: 99%

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confidence: 99%

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-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

2015

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“…A number of agents have been used with varying success to pharmacologically raise HbF with tolerable adverse effects (reviewed in Ref. 65). Results to date have generally been disappointing.…”

Section: Fetal Hemoglobin Inductionmentioning

confidence: 99%

Thalassemia 2016: Modern medicine battles an ancient disease

Rund

2015

American J Hematol

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Thalassemia was first clinically described nearly a century ago and treatment of this widespread genetic disease has greatly advanced during this period. DNA‐based diagnosis elucidated the molecular basis of the disease and clarified the variable clinical picture. It also paved the way for modern methods of carrier identification and prevention via DNA‐based prenatal diagnosis. Every aspect of supportive care, including safer blood supply, more regular transfusions, specific monitoring of iron overload, parenteral and oral chelation, and other therapies, has prolonged life and improved the quality of life of these patients. Significant advances have also been made in allogenic bone marrow transplantation, the only curative therapy. Recently, there has been a rejuvenated interest in studying thalassemia at the basic science level, leading to the discovery of previously unknown mechanisms leading to anemia and enabling the development of novel therapies. These will potentially improve the treatment of, and possibly cure the disease. Pathways involving activin receptors, heat shock proteins, JAK2 inhibitors and macrophage targeted therapy, among others, are being studied or are currently in clinical trials for treating thalassemia. Novel types of genetic therapies are in use or under investigation. In addition to the challenges of treating each individual patient, the longer survival of thalassemia patients has raised considerations regarding worldwide control of thalassemia, since prevention is not universally implemented. This review will trace a number of the original medical milestones of thalassemia diagnosis and treatment, as well as some of the most recent developments which may lead to innovative therapeutic modalities. Am. J. Hematol. 91:15–21, 2016. © 2015 Wiley Periodicals, Inc.

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“…Patients who have sickle cell/β-thalassemia typically have symptoms similar to sickle cell anemia, though the intensity of the anemia can vary depending on the severity of the thalassemia [12]. Increased research in population genetics of hematological disorders over the past few years have enabled better understanding of the genetic factors responsible for progression and severity of anemia in Hb E/β-thalassemia [13]. The type of β-thalassemia mutation co-inherited with Hb E, the co-inheritance of alpha (α) thalassemia, and polymorphisms associated with increased synthesis of fetal hemoglobin; are some of the genetic factors influencing the clinical course of this disease [14].…”

Section: Discussionmentioning

confidence: 99%

Prenatal Screening for Co-Inheritance of Sickle Cell Anemia and β-Thalassemia Traits

Dhawan¹,

Chaudhary²,

Chandratre³

et al. 2016

Clin Med Biochemistry Open Access

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Co-inheritance of sickle cell anemia and β-thalassemia traits require medical attention. Individuals with sickle cell and β-thalassemia disorders produce abnormal form of hemoglobin or decreased synthesis or complete absence of the β-globin chains of hemoglobin. Therefore, affected individuals might require blood transfusions at regular intervals. Prenatal diagnosis of fetal hemoglobinopathy should be offered when the fetus is at risk of being affected. The aim of this study was to assess the applicability of the nucleotide sequencing method in the identification of both diseases and to identify and counsel asymptomatic parents to make reproductive choices. We demonstrate the ability to detect these traits in a family, which was suspected to be carrying β-thalassemia mutations as per the clinician.

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Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

Cited by 176 publications

References 136 publications

-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies

Thalassemia 2016: Modern medicine battles an ancient disease

Prenatal Screening for Co-Inheritance of Sickle Cell Anemia and β-Thalassemia Traits

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