In Vitro Hb Production in B-thalassemia Patients Is Not a Predictor of Clinical Responsiveness to Hydroxyurea

Overview

Journal Iran J Public Health

Date 2017 Aug 29

PMID 28845406

Citations 2

Authors

Mohammad Reza Mahdavi

Farzin Pourfarzad

Mehrnoush Kosaryan

Mohammad Taghi Akbari

Affiliations

Soon will be listed here.

Abstract

Background: The hematologic response to hydroxyurea (HU) is varied among β-thalassemia (BT) patients. The BCL11A and SOX6 genes are involved in response to HU. This study aimed to investigate the in-vitro responsiveness of HU among BT major patients homozygote for IVSII-1G>A mutation and XmnI single nucleotide polymorphism (SNP) in order to find whether the in-vitro Hb concentration is a predictor of clinical (HU) responsiveness.

Methods: In this case-control study, twenty BT patients homozygote for IVSII-1G>A mutation and XmnI SNP from Thalassemia Research Center, Sari, Iran in 2015 were selected and categorized into two groups of 10 Responder (R) and 10 Non-Responder (NR) according to their clinical HU response. Ten healthy individuals as a control group were also selected. Hematopoietic erythroid progenitors were expanded from peripheral blood. Hb concentration was measured using photometry method. The flow cytometry and real-time PCR methods were applied for the analysis of cell surface markers (CD71 and CD235a) and gene expression (BCL11A and SOX6), respectively.

Results: R and NR groups produced higher amount of Basic Hb than C group in cell culture medium at day 14 (<0.05). After HU treatment, in R group, Hb levels was significantly elevated in comparison to NR and C group (<0.05). BCL11A expression was decreased after exposure to HU in all groups while SOX6 expression was only down-regulated in C group, and its expression was increased in R and NR groups after HU treatment.

Conclusion: Since different factors including wide networks of intracellular factors and individual differences between patients can affect response to HU in patients, the increasing Hemoglobin on culture medium alone cannot predict clinical responsiveness to that drug.

Citing Articles

Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.

Diamantidis M, Ikonomou G, Argyrakouli I, Pantelidou D, Delicou S Int J Mol Sci. 2024; 25(22).

PMID: 39595957 PMC: 11593634. DOI: 10.3390/ijms252211886.

Epigenetic Insights and Potential Modifiers as Therapeutic Targets in -Thalassemia.

Zakaria N, Islam M, Abdullah W, Bahar R, Yusoff A, Abdul Wahab R Biomolecules. 2021; 11(5).

PMID: 34070036 PMC: 8158146. DOI: 10.3390/biom11050755.

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