Multiple Myeloma in Taiwan- Epidemiology, Cytogenetics, Molecular Cytogenetics and Animal Model
Date Issued
2006
Date
2006
Author(s)
DOI
zh-TW
Abstract
This is the first time that serial studies on multiple myeloma (MM) conducted in Taiwan. There are three components in the thesis: epidemiology of MM in Taiwan for the past two decades, conventional cytogenetics and fluorescence in-situ hybridization analyses on our MM patients and a new nod-SCID/human chimeric animal model for MM.
From the descriptive epidemiological study on MM in Taiwan, it is known that the incidence and mortality rates of MM keep increasing for the past two decades. The crude incidence rates per 100,000 persons of MM were 0.16 in 1979 and 1.29 in 2001. The average age-adjusted (1976 and 2000 world population) incidence rates of MM in Taiwan for 1979-2001 were 0.61 and 0.65 per 100,000 persons, respectively. The average age-adjusted (1976 and 2000 world population) mortality rates of MM were 0.49 and 0.55 per 100,000 persons, respectively. The average male-to-female incidence ratio was 1.68:1. The incidence of MM peaked at the seventh decade. Of the hospital MM patients, the clinical characteristics and treatment outcome were similar to western countries. The overall survival, 10-year survival were 28 months and 7.3%, respectively. Agriculture was likely to associate with occurrence of MM. Higher incidence of extramedullary MM in younger patients were noted.
Cytogenetic anomalies (CA) were detected by conventional cytogenetics (CG) (CG_CA) in 44 (29.3%) of the 150 patients and by FISH (FISH_CA) in 59 (67.0%) of the 88 studied patients. Presence of either CG_CA or FISH_CA was associated with a poor prognosis. Patients with CG_CA and hyperdiploid chromosomes, always associated with several trisomies, had a longer survival in comparison to those with non-hyperdiploid chromosomes, usually associated with a monosomy 13/partial deletion of 13q (Δ13) and a rearrangement of 14q32. A novel recurrent CG_CA, add (19)(p13), was found in four patients; all males with immunoglobulin G/λ isotypes, extramedullary myeloma at diagnosis, and a poor prognosis. Three groups of patients with significantly different survival, CG_Δ13, FISH_Δ13 but without CG_Δ13, and neither CG_Δ13 nor FISH_Δ13 were identified.
The NOD/SCID human chimeric animal model was generated by implanting of human fetal bones (FBs) into subcutaneous sites of NOD/SCID mice, followed by inoculation of primary bone marrow mononuclear cells obtained from patients with MM into the FBs. Most of them revealed evidence of tumor growth of myeloma cells in the NOD/SCID-hu+ mice and some would develope not only myeloma in the BM of the FBs, but also extramedullary macro-tumors (EMTs) along the periosteum of the FBs. The tumor cells in these EMTs had plasmacytoid morphology and preserved antigens and cytogenetics similar, if not identical, to those in the parent MCs. The NOD/SCID-hu chimeric animal model is highly efficient for growth of primary MCs and presents clinical features of human MM. The engrafted MCs can be maintained subsequently in NOD/SCID-hu- mice as in vivo culture.
Subjects
多發性骨髓瘤
流行病學
細胞遺傳學
動物模式
multiple myeloma
epidemiology
Taiwan
cytogenetics
animal model
SDGs
Type
text
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