Pathogenesis and progression of malignant B cell neoplasms
Abstract of thesis entitled Pathogenesis and progression of malignant B cell neoplasms
Submitted by Au Wing Yan
For the degree of Doctor of Medicine
at the University of Hong Kong
The spectrum of B cell malignancies recapitulates the different stages of B cell development. However, the underlying pathogenetic cause is diverse and largely unknown. This thesis presents a combination of origin epidemiological, cytogenetic and molecular genetic data from the author's experience in Hong Kong and Vancouver to uncover new leads in the field.
Our migrant studies in Chinese to Canada suggested that the incidence and subtypes of non-Hodgkin lymphoma is largely preserved. However, Hodgkin lymphoma rates tend to rise towards Canadian freqeuncies. This reflects the relative contribution of genetic and environmental factors in the two diseases.
Different lymphomas carry hallmark (primary) translocations. Our cytogenetic work suggest that most mantle cell lymphomas carried t(l 1 ;14) and follow distinct evolution patterns, while t(14;18) is overwhelmingly present in Chinese follicular lymphoma. We explored the breakpoint variety involving the bcl-6 gene in a wide spectrum of B cell neoplasms, and reconfirmed the specific association of bcl-3 with atypical chronic lymphocytic leukemia. For secondary cytogenetic changes, the drastic clinical impact of an acquired 8q24 aberration is illustrated. Two unique cases of transformed plasma cell leukemia and diffuse large cell lymphoma demonstrated molecular lineage contiuity in B cell neoplasms despite histological transformations under selection pressure. Using epigenetic methylation studies in gastric and therapy related lymphomas, we were able to subclassify them into different pathogenetic subgroups. Studies on background genetic predisposition to B cell neoplasms was less fruitful, although we showed increased risks in patients with ankylosing spondylitis and HLA B27, and also an association between TNF -308G/A polymorphism and poor prognosis in Chinese plasma cell myeloma. Finally, two infective agents, Epstein Barr virus (EBV) and Helicobacter pylori are causatively linked to 10-20% of all B cell lymphomas and 60-90% of all gastric lymphomas. Data on their detection by polymerase chain reaction and specific serology in Chinese are updated.
Word count 300 Signature of candidate
School:The University of Hong Kong
School Location:China - Hong Kong SAR
Source Type:Master's Thesis
Keywords:b cells tumors lymphomas genetic aspects cytogenetics molecular genetics
Date of Publication:01/01/2005