Genetic Modifiers of Foetal Haemoglobin in Haematological Malignancies
Research type
Research Study
Full title
Genetic modifiers of foetal haemoglobin and response to pharmacological induction in various haematological malignancies and sickle cell disease: A cross-sectional and cohort study.
IRAS ID
151397
Contact name
Swee Lay Thein
Contact email
Research summary
Increasing levels of fetal haemoglobin (HbF) have significant ameliorating effects on patients with sickle cell disease (SCD) and ß-thalassaemias.
Genetic studies have identified three genes: (Xmn1 HBG2, BCL11A, and HBS1L MYB (HMIP)) as consistently associated with HbF. Recently, the HMIP HbF gene has been shown to influence different haematological parameters including total haemoglobin and monocytes.
Three chemotherapeutic agents: Hydroxycarbamide, 5-Azacytidine, and Lenalidomide have been shown to therapeutically induce HbF levels in SCD and ß-thalassaemias. These same agents are utilised as chemotherapy for haematological malignancies: a) Myeloproliferative neoplasms (MPN), b) Myelodysplastic syndrome (MDS), and c) Myeloma respectively. Response to these agents within this context involves an increase in total haemoglobin and improvement in other haematological parameters. However, unlike in SCD, the HbF induction profile has not been well studied in haematological malignancies.
We propose that these HbF genes influence response to the aforementioned chemotherapeutic agents in the three haematological malignancies as measured by changes in HbF percentage, total haemoglobin and other haematological parameters. If so, a delineation of the HbF genes could allow a prediction of response to chemotherapeutic agents in haematological malignancies.
Part A - we will recruit adult patients with the above haematological malignancies who are already taking the above chemotherapeutic agents. Adult patients, with the same haematological malignancies, who are not taking chemotherapy, will be recruited as a control group. We will collect a blood sample to measure specific haematological parameters including HbF % and genetic analysis to determine HbF genes.
Part B – we will recruit patients with haematological malignancies who will be commencing chemotherapy. In each patient, pre- treatment and post treatment levels of HbF %, HbF genes and other haematological parameters will be monitored. Patients will be followed up for one year post-treatment. Chromosomal abnormalities of these haematological malignancies will also be assessed in all patients.
REC name
Wales REC 4
REC reference
14/WA/1078
Date of REC Opinion
31 Jul 2014
REC opinion
Favourable Opinion