Home
Who Are We?
Clinical Unit
Research Unit
Achievements
Group Meetings
Collections
Events
How To Help
Contact Us
Links

The Research Unit

The MLGS did fund a Research Laboratory at the hospital, although this has now been mothballed by the Taunton and Somerset NHS Trust. The results of the research at Musgrove have been published in international journals, increasing world-wide knowledge of the leukaemic process. Having this research based locally has the additional advantage of increasing the range of tests available to consultants at Musgrove to help guide them with the treatment of current patients with all types of leukaemia and lymphoma.

A brief description of the past leukaemia research project funded by MLGS

Blood is made up of many different types of cells all designed to carry out a particular function. Red blood cells carry oxygen around the body and platelets help with blood clotting. The white blood cells or leucocytes can be divided into 3 main groups, granulocytes, monocytes and lymphocytes. The B-lymphocytes and T-lymphocytes are involved with fighting infections. During a person's lifetime many billions of these blood cells are produced to replace cells that have reached the end of their lifespan. In fact 3 million red blood cells and 120,000 white blood cells are produced every second.

All these different blood cells come from very rare primitive cells called 'stem cells'. These stem cells are not only capable of maturing into the different types of blood cells but are also capable of 'self-renewal' and are therefore able to remain as stem cells.

In healthy individuals the numbers and distribution of the different types of blood cells shows very little variation. This would indicate that the rate at which new blood cells are produced and old blood cells are destroyed is under tight regulation. However, if someone has leukaemia, this regulation has broken down and too many cells of one type are present. If the abnormal cells are immature the leukaemia will be an acute form such as Acute Myeloid Leukaemia, whereas if the cells are mature the leukaemia will be a chronic form such as Chronic Lymphocytic Leukaemia.

A hallmark of all cancers, including leukaemia, is the capacity for cells to undergo unlimited self-renewal, like stem cells. It has been proposed that either leukaemias could arise from 'faulty' blood stem cells or alternatively from a more mature, differentiated blood cell that has re-acquired stem cell characteristics. The scientists at Musgrove Park Hospital are currently investigating the possibility that in Chronic Lymphocytic Leukaemia one of the genetic pathways involved in self-renewal of stem cells has been 'switched back on' in mature B-lymphocytes.

The factors that control the process of stem cell self-renewal are still being discovered but some of the key elements are already known. We are looking at these elements in leukaemic cells and comparing them to normal blood cells. A pilot study funded by the MLGS in 2004/05 has already yielded some interesting results in this area and the Research Laboratory is continuing this work in 2005/06 in order to gain further insight into the regulation of this important pathway in low-grade B cell malignancies.

The Research Laboratory has now taken delivery of a Polymerase Chain Reaction (PCR) machine, funded by the MLGS. Polymerase Chain Reaction is a rapid way to identify leukaemia and lymphoma cells in patients. Real Time PCR uses fluorescent dye chemistry to accurately monitor the reaction in its early stages. Real Time PCR assesses the level of the disease still present after chemotherapy and the technology allows a greater sensitivity of detection and the ability to monitor whether the level of the leukaemic clone is increasing or decreasing. Real Time PCR will greatly help the service provided to patients at Musgrove Park Hospital.

 

Publications

Howe D, Hopkins J, Johnson S and Phillips M (1993). Simultaneous analysis of cell surface antigens and DNA content by flow cytometry. Clinical and Laboratory Haematology, 15, 113-118.

Johnson S, Richardson D, Hopkins J, Howe D and Phillips M (1993). Complete remission after fludarabine for chronic lymphocytic leukaemia. Blood, 81, 560.

Richardson D, Johnson S, Hopkins J, Howe D and Phillips M (1994). Absence of minimal residual disease detectable by FACS, Southern blot or PCR in patients with chronic lymphocytic leukaemia treated with fludarabine. Acta Oncologica, 33 (6), 627-30.

Cull G, Howe D, Stack-Dunne M, Phillips. M. J and Johnson, 5 (1995). Tetrasomy of chromosome 8 in a patient with acute myeloid leukaemia. Leukemia and Lymphoma, 19, 355-358.

Cull G, Richardson D, Howe D, Hopkins J, Johnson S and Phillips, M (1995) Molecular complete response in a patient with chronic lymphocytic leukaemia treated with 2-Chlorodeoxyadenosine. Acta Oncologica, 34(4), 531-537.

Lynas C, Howe D, Sweeny M and Wagstaff, M (1995). t(8;2 1) detection by RT-PCR: an improved primer set convenient for the routine laboratory. British Journal of Haematology, 91, 924-926.

Bromidge T, Howe D, Johnson S and Phillips M (1995). Adaptation of the TdT assay for semi-quantitative flow cytometric detection of DNA strand breaks.
Cytometry, 20, 257-260.

Lynas C, Howe D, Copplestone J, Johnson S and Phillips M (1995). A rapid and reliable PCR method for detecting clonal T-ce1l populations. Journal of Clinical Pathology: Molecular Pathology. 48, M101-M104.

Lynas C, Howe D, Sweeny M and Wagstaff M (1996). Further improvement of the t(8;2 1) detection by RT-PCR. British Journal of Haematology, 94, 422.

Lynas C and Howe D (1997). Additional TCRVbeta primers and minor method modifications improve detection of clonal T-cell populations by RT-PCR. Molecular Pathology, 50 (1), 53-55.

Bromidge T, Howe D, Johnson S and Rule S (1997). Heterogeneity of clonal lymphocytes with regard to bcl-2 protein concentration and cell size. Molecular Pathology, 50 (6), 326-328.

Howe D, Bromidge T, Stack-Dunne M, Davies S, Paxton A, Phillips M, Rule S and Johnson S (1997). Trisomy 12 is a rare event in cases of CLL with typical immunophenotype and morphology. Hematology, 2 , 373-378.

Lynas C and Howe D (1998). Simple, reliable detection of T-cell clones by PCR-LIS-SSCP analysis of TCR gamma rearrangement. Molecular and Cellular Probes, 12, 4148.

Macey M, Hou L, Milne T, Parameswarren V, Howe D, Cavenagh J, Howells G and Newland A (1998) A CD4+ proliferation of large granular lymphocytes expresses the protease activated receptor-1. British Journal of Haematology,101, 78-81.

Bromidge T D Turner D Howe, D Johnson S and Rule S(1998). In vitro chemosensitivity of chronic lymphocytic leukaemia to purine analogues - correlation with clinical course. Leukemia, 12, 1230-1235.

Smith P, Cavenagh J D, Milne T, Howe D, Wilkes S J, Sinnott P, Forster G E & Helbert M. Benign monoclonal expansion of CD8+ lymphocytes in HIV infection. Journal of Clinical Pathology 2000; 53 (3): 177-181.

Bromidge J & Howe D. Screening of the entire coding region of p53 in low grade lymphoproliferative disorders. Journal of Clinical Pathology: Molecular Pathology, 2000; 53 (4): 216-218.

Howe D & Lynas C. The cyclin D1 alternative transcripts [a] and [b] are expressed in normal and malignant lymphocytes and their relative levels are influenced by the polymorphism at codon 241. Haematologica, 2001; 86 (6): 563-569.

Bromidge T, Lynas C. Relative levels of alternative transcripts of the ING1 gene and lack of mutations of p33/ING1 in haematological malignancies. Leukemia Research 2002, 26(7): 631-5.

Bromidge T, Lowe C, Prentice A, Johnson S. p53 intronic point mutation, aberrant splicing and telomeric associations in a case of B-chronic lymphocytic leukaemia. British Journal of Haematology 2000, 111 (1): 223-229.