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Tetraspanins as therapeutic targets in hematological malignancy: a concise review.

ABSTRACT: Tetraspanins belong to a family of transmembrane proteins which play a major role in the organization of the plasma membrane. While all immune cells express tetraspanins, most of these are present in a variety of other cell types. There are a select few, such as CD37 and CD53, which are restricted to hematopoietic lineages. Tetraspanins associate with numerous partners involved in a diverse set of biological processes, including cell activation, survival, proliferation, adhesion, and migration. The historical view has assigned them a scaffolding role, but recent discoveries suggest some tetraspanins can directly participate in signaling through interactions with cytoplasmic proteins. Given their potential roles in supporting tumor survival and immune evasion, an improved understanding of tetraspanin activity could prove clinically valuable. This review will focus on emerging data in the study of tetraspanins, advances in the clinical development of anti-CD37 therapeutics, and the future prospects of targeting tetraspanins in hematological malignancy.

SUBMITTER: Beckwith KA

PROVIDER: S-EPMC4369647 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Tetraspanins as therapeutic targets in hematological malignancy: a concise review.

Beckwith Kyle A KA Byrd John C JC Muthusamy Natarajan N

Frontiers in physiology 20150323

Tetraspanins belong to a family of transmembrane proteins which play a major role in the organization of the plasma membrane. While all immune cells express tetraspanins, most of these are present in a variety of other cell types. There are a select few, such as CD37 and CD53, which are restricted to hematopoietic lineages. Tetraspanins associate with numerous partners involved in a diverse set of biological processes, including cell activation, survival, proliferation, adhesion, and migration. ...[more]

PMID: 25852576

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Project description:The objective of this study was to explore the following aspects of teicoplanin use in patients with hematological malignancy: early attainment of target trough concentrations with current high-dose teicoplanin regimens, variability in unbound teicoplanin fractions, factors associated with observed total and unbound trough concentrations, efficacy and toxicity, and renal function estimation. This was a single-center, prospective study. Samples for determination of trough concentrations were taken on days 3, 4, 7, and 10. Total and unbound teicoplanin concentrations were determined using validated high-performance liquid chromatography methods. Regression analyses were used to identify the factors associated with the trough concentration. Thirty teicoplanin-treated adults with hematological malignancy were recruited. Despite the use of dosages higher than the conventional dosages, the proportions of patients with a trough concentration of ?20 mg/liter at 48 h and at 72 h were 16.7% and 37.9%, respectively. Renal function was significantly negatively associated with total trough concentrations at 48 h and 72 h (P < 0.05). For an average hematological malignancy patient (creatinine clearance = 70 ml/min), sequential loading doses of at least 12 mg/kg of body weight may be needed to achieve early adequate exposure. In the absence of measured creatinine clearance, estimates obtained using the Cockcroft-Gault (total body weight) equation could prove to be an acceptable surrogate. The unbound fractions of teicoplanin were highly variable (3.4 to 18.8%). Higher unbound fractions were observed in patients with low serum albumin concentrations. Teicoplanin was well tolerated. Teicoplanin loading doses higher than those in current use appear to be necessary. Increased dosing is needed in patients with increased renal function. The high variability in protein binding supports the contention for therapeutic drug monitoring of unbound teicoplanin concentrations. (This study has been registered with EudraCT under registration no. 2013-004535-72.).

Dataset Information

Tetraspanins as therapeutic targets in hematological malignancy: a concise review.

Publications

Tetraspanins as therapeutic targets in hematological malignancy: a concise review.

Similar Datasets

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