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Feb 2014 DOI 10.14302/issn.2372-6601.jhor-13-346
E. Clapham ChloeCorresponding author
Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK
Targeting cell metabolism is a therapeutic approach which has been used for the treatment of cancers with high levels of proliferation. Inhibition of metabolic processes in cancer cells has shown synergy with current therapeutic options to reduce refractory disease and relapse. In contrast, chronic lymphocytic leukaemia (CLL) is a disease where expansion of the malignant clone results from a combination of enhanced cell survival coupled with low level proliferation. The purpose of this article is to highlight how further research is needed to determine whether targeting cell metabolism may be a viable therapeutic strategy in this disease. We discuss how lymphocyte doubling time (LDT) remains a robust prognostic indicator used in the current clinical management of CLL, and how recognition of CLL as a proliferative disease has led to a greater understanding of the importance of energy-generating processes in its pathobiology. We summarize what is currently known about normal B cell metabolism and consider whether there is evidence of the Warburg effect in CLL cells. Finally, we speculate on how CLL cells may exploit protective mechanisms such as autophagy during times of metabolic stress and how they might influence or be influenced by metabolic characteristics of the microenvironment.
Nov 2018 DOI 10.14302/issn.2689-5773.jcdp-18-2435
Bajaj AnubhaCorresponding author
Consultant Histopathologist
Theobjective of reviewing Hairy Cell Leukaemia may be achieved by emphasising the condition as a category of chronic lymphocytic leukaemia with hair like protrusions of the cytoplasm situated on the aberrant B cell surface. An infrequent disorder, hairy cell leukaemia contributes an estimated 2% of lymphoid malignancies with a male predominance ( M:F ::4-5:1). A majority (90%) of instances depict a mutant immunoglobulin heavy chain variable region (IGHV). The haematopoietic stem cells (HSCs) elucidate a B raf proto-oncogene( BRAF V600E gene- 7q34). An enlarged spleen may be discerned along with pancytopenia as a presenting symptom. The morphology of specific hairy cell leukaemia may be on account of an in vitro interaction of primary hairy cells with BRAF genes and MEK inhibitors, which incite a prominent MEK - ERK dephosphorylation, thereby curtailing transcriptional outpourings of the RAS- RAF- MEK-ERK pathway. Bone marrow aspiration or bone marrow trephine biopsy may be inadequate for diagnosis in 30%-50% individuals on account of extensive fibrosis and the bone marrow sections depict a characteristic interstitial infiltration of leukaemia cells.. Reticulin stains exhibit broad, dense reticulum fibres surrounding the individual or aggregates of leukaemia cells with fibrotic extensions into the abutting bone marrow. The immune reactivity of classic hairy cell leukaemia is concurrent CD19+ CD20+,CD 11c+, CD25+, CD103+ and CD123+. Immune staining for CD20+, annexin 1 and VE1 (a BRAF V600E stain) validates the diagnosis and analyses the extent of malignant bone marrow infiltration. Application of inhibitors of BRAF V600E gene is efficacious in patients resistant to standard therapy. An enlarged spleen beyond 3 centimetres of the left costal margin, a white blood cell count greater than 10000 cells/µL , circulating hairy cells in the peripheral blood greater than 5000 cells/µL and a β 2 micro-globulin level exceeding twice the normal range of 3 µg/ml delineate an inferior outcome with resistance to purine analogues (PNAs). CD38+ elucidation ensures a worse prognosis as does the lack of an IGHV mutation with a reduced overall survival,. A lack of BRAF genetic mutation in 10% -20% of hairy cell leukaemia comprises of inferior prognosis.
Feb 2017 DOI 10.14302/issn.2372-6601.jhor-17-1423
YA Dei-AdomakohCorresponding author
Departments of Haematology
Background: The diagnosis and treatment outcomes of Non- Hodgkin Lymphoma’s (NHL) in resource poor countries in the absence of routine molecular studies and immunohistochemistry is challenging. Methods: A retrospective review of case folders of NHL patients aged13 years and above. Information obtained from the case folders included age, sex, histological subtype, subtypes using the Working Formulation and WHO classifications. Treatment given and follow up information were also evaluated. Results: A total of 279 cases of NHL were identified within the study period. The mean age of the patients was 48.8 ± 17.0 years. The male to female ratio was approximately 1.5:1. The majority of cases seen (53%) were diffuse large B- cell lymphoma. Chronic lymphocytic leukaemia/ small lymphocytic lymphoma (22.2%) was the next most common subtype. Other sub types seen, in order of frequency, included diffuse mixed cell lymphoma (6.4%), gastric lymphomas (3.9%), mediastinal B- cell lymphoma (2.9%), Burkitt’s lymphoma (1.8%), splenic marginal zone B-cell lymphoma (1.1%), lymphoblastic lymphoma (1.1%), mucosa- associated lymphoid tissue (MALT) type B- cell lymphoma (0.7%) and follicular lymphoma (0.7%). Conclusion: This study provides an overview of the distribution of NHL subtypes and their outcomes in a resource constrained setting. Immunohistochemistry, cytogenetics and specific molecular studies which are important in characterization of NHLs, should be made affordable and accessible in low income countries.