Combined Morphological and Interphase Fluorescence in Situ Hybridization Study in Multiple Myeloma of Chinese Patients

Abstract

To gain insight into the real incidence of the numeric chromosomal aberrations and the cell lineage involvement of the neoplastic process in multiple myeloma (MM) , we examined 18 Chinese MM patients by May-Grunwald-Giemsa (MGG) staining and fluorescence in situ hybridization using three DNA centromeric probes specific for chromosomes 3 , 7 , and 9. In this investigation , cytogenetic abnormalities were detected in plasma cells (PCs) , myeloid cells (MCs), and lymphoid cells (LCs) in all of the MM patients studied. This is the first demonstration of the cytogenetic aberration involved in the myeloid series. Multiple myeloma (MM) has been regarded as the neoplastic disease of the terminally differentiated B cell with elusive oncogenesis. Although the majority of the tumor cells found in the bone marrow can be recognized by their typical plasma cell morphology, they are the progeny of a yet unidentified myeloma progenitor cell. Suggested possibilities of this clonogenic cell include peripheral blood B-lymphoid cell, pre-B cell, and hematopoietic stem cell.1 Thus far, knowledge on the nature and development of the clonogenic cell has been lacking. This shortcoming has been an obstacle to rational intervention and contributed to a high fatality of MM from ineffective treatment.The low proliferative rate of the tumor cells in this malignancy has hampered the conventional cytogenetic analysis. An abnormal karyotype, often a complex mixture of numeric and structural changes, is found in ϳ50% of patients.2 Recent data have revealed that 55% of MM patients had three or more trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21. 3 The significance of these chromosomal aberrations in MM pathogenesis remains obscure. As a large number of proliferating or nondividing cells can be examined, use of fluorescence in situ hybridization (FISH) has improved the detection of cytogenetic abnormalities in MM. In addition, by combination with morphological assessment of the cells studied, the lineage of cells that are involved in the neoplastic transformation can be elucidated. Using FISH and 10 ␣-satellite DNA probes, Drach et al 4 showed that 88.9% of MMs were aneuploid for at least one chromosome examined and 66% had aberrations in three or more chromosomes. In the same study, mature myeloid cells evaluated showed no abnormality. 4 After FISH procedure, cytomorphological details are so obscured that it would be very difficult to ascertain the cell types being assessed. Using combined morphological and FISH

Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays

“…A recent study has revealed that BMI-1 is a transcription repressor that targets the ink4a locus, which encodes the p16 protein and that BMI-1 cooperates with c-myc by repressing p16 and P19/ ARF. Of note, the p16 protein is often absent in myeloma cells (Ng et al, 1997). Though a promoter hypermethylation has been invoked, our data suggest that BMI-1 could contribute to p16 silencing in MM.…”

Early acquisition of homozygous deletions of p16/p19 during squamous cell carcinogenesis and genetic mosaicism in bladder cancer

“…Methylation of the 5'CpG island of p16 is another mechanism for inactivation of this gene, and several tumors have been reported to show this alteration Gonzalez-Zulueta et al, 1995a;Fueyo et al, 1996;Wong et al, 1997;Ng et al, 1997;Herman et al, 1997). In this report, methylation of p16 promoter was analysed in 15 tumor specimens from ten bladder cancer patients as well as seven squamous metaplasia specimens from two bladder cancer patients and ®ve cancer free patients.…”

“…These two genes are frequently deleted in several kinds of tumors (Kamb et al, 1994;Nobori et al, 1994;Cairns et al, 1995). De novo methylation of the 5'CpG island in the promoter of p16, which inhibits the expression of p16 but not p19 Gonzalgo et al, 1998), is another mechanism of the gene silencing, and has been reported to occur frequently in a variety of cancers Fueyo et al, 1996;Gonzalez-Zulueta et al, 1995a;Wong et al, 1997;Ng et al, 1997;Herman et al, 1997).…”

The Multiparametric Scanning System for Evaluation of Minimal Residual Disease in Hematological Malignancies

“…Recently various methods were developed for the combination of MGG staining with FISH at the single cell level such as the manual search for PC [27], the combined immunofluorescent PC detection and FISH [23, 24, 26]and the purification of PC with anti-CD138-coated magnetic beads [25, 28]. All these methods are time-consuming, may lead to loss of PC, and have limitations related to immunofluorescent PC detection, allowing only the analysis of BM samples with >30% of PC.…”