Humans ; Multiple Myeloma/genetics* ; Neoplasm, Residual/diagnosis* ; Flow Cytometry ; High-Throughput Nucleotide Sequencing

OBJECTIVETo analyze the cytogenetic abnormalities and prognostic outcomes of patients with multiple myeloma (MM) detected by fluorescence in situ hybridization (FISH).

METHODSThe clinical record of 117 newly-diagnosed patients with MM treated in department of hematology and geriatric hematology of our hospital for 7 years were collected, and their molecular cytogenetic abnormalities detected by FISH and the clinical outcome were analyzed retrospectively.

RESULTSThe detected rate of cytogenetic abnormality was 76.9%(90/117), the most common abnormality deteted by FISH was 1q21+ (71.1%), followed by 13q- (56.6%). The cross comparison method showed that 13q- and 17p13-, t(11;14) and t(4;14) were related respectively. All the patients with cytogenetic abnormalities showed no significant difference in the overall survival from cytogenetic normal patients.

CONCLUSIONThe positive rate of molecular cytogenetic abnormalities detected by FISH in MM patients is high, but data from larger and longer studies are needed to evaluate the prognostic outcomes.

Chromosome Aberrations ; Chromosome Deletion ; Cytogenetics ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; diagnosis ; genetics ; Prognosis ; Retrospective Studies ; Translocation, Genetic

BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calcium/blood ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 4 ; Creatine/blood ; Female ; Hemoglobins/analysis ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/genetics/mortality ; Multivariate Analysis ; Prognosis ; Survival Rate ; Young Adult

OBJECTIVETo assess the correlation of cytogenetic changes with serum vascular endothelial growth factor (VEGF) and serum tartrate resistant acid phosphatase (TRacp-5b) levels among elderly patients with multiple myeloma (MM).

METHODSChromosomal changes were analyzed with a modified culturing method in the presence of IL-6. Serum levels of VEGF and TRacp-5b were determined with enzyme-linked immunosorbent assays (ELISA).

RESULTSAmong the 60 MM patients, chromosomal abnormalities were found in 27 cases, including 22 with numerical abnormalities and 15 with structural abnormalities. Many patients had both numerical and structural abnormalities. For 33 patients with a normal karyotype, the levels of VEGF and TRacp-5b were 117.35 ± 55.26 pg/mL and 4.15 ± 2.15 U/L, respectively, while for 27 patients with an abnormal karyotype, the levels of VEGF and TRacp-5b were 190.26 ± 85.74 pg/ml and 5.96 ± 2.24 U/L, respectively. The difference between the two groups was significant (P<0.05).

CONCLUSIONCompared with MM patients with a normal karyotype, the levels of VEGF and TRacp-5b are higher in those with cytogenetic abnormalities.

Aged ; Aged, 80 and over ; Chromosome Aberrations ; Cytogenetic Analysis ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Male ; Multiple Myeloma ; blood ; diagnosis ; genetics ; Tartrate-Resistant Acid Phosphatase ; blood ; Vascular Endothelial Growth Factor A ; blood

No abstract available.
Aged ; Antineoplastic Agents/therapeutic use ; Bone Marrow/pathology ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications/*diagnosis/drug therapy ; Leukocyte Count ; Male ; Multiple Myeloma/complications/*diagnosis/drug therapy ; Platelet Count ; Polymerase Chain Reaction ; Thrombocytosis/etiology

OBJECTIVETo explore the application of BIOMED- 2 standardized immunoglobulin (Ig) gene rearrangement system in the diagnosis of multiple myeloma (MM), and the significance of clonality analysis by multiplex-PCR amplifications.

METHODSA total of 167 cases of MM bone marrow samples from 2009 to 2013, and 20 cases of reactive plasmacytosis used as the controls were included in this study. Multiplex-PCR amplifications were performed and the Ig gene rearrangements were analyzed using BIOMED-2 standardized clonality analysis system.

RESULTS① Of 167 MM cases, 107 showed IgH VH-JH rearrangement, 33 showed IgH DH-JH rearrangement, and 30% showed IgH DH-JH rearrangement in 60 IgH VH-JH rearrangement negative MM cases. The difference was statistically significant between IgH VH-JH rearrangement positive and negative cases (14.0% vs 30.0%, P=0.032). The total positive rate of IgH VH-JH, IgH DH-JH and IgK was 94.6%. The 20 reactive plasmacytosis (RP) cases showed negative Ig gene rearrangement. 2 of 167 MM cases, 9 (5.4%) showed clonal IgH rearrangement by agarose electrophoresis were confirmed as polyclonality by capillary electrophoresis. ③ Of 53 MM cases who have been detected by Ig gene rearrangement system and fluorescence in situ hybridization (FISH) for IgH simultaneously, 36 showed IgH rearrangement, 26 showed FISH IgH positive, and the difference was statistically significant (67.9% vs 49.1%, P=0.049).

CONCLUSIONCombined detection of IgH VH- JH, IgH DH- JH and IgK could improve the positive rate of MM clonality dramatically, and measurement of IgH DH-JH rearrangement was more important in the IgH VH- JH negative cases. Ig gene rearrangement system was a faster and more sensitive method than FISH IgH. Application of BIOMED- 2 standardized immunoglobulin (Ig) gene rearrangement system is of significance for MM diagnosis.

Humans ; Immunoglobulins ; genetics ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; diagnosis ; genetics ; Polymerase Chain Reaction ; V(D)J Recombination

No abstract available.
Adult ; Aged ; Base Sequence ; Bone Marrow/metabolism/pathology ; Female ; Formaldehyde/chemistry ; Gene Frequency ; Humans ; Male ; Middle Aged ; Multiple Myeloma/diagnosis/genetics ; Mutation ; Myeloid Differentiation Factor 88/chemistry/*genetics/metabolism ; Paraffin Embedding ; Sequence Analysis, DNA/*methods ; Waldenstrom Macroglobulinemia/diagnosis/genetics

OBJECTIVETo explore the deletion rate, clinical correlation and prognostic significance of 1p21 deletion, a novel genetic prognostic index, in patients with multiple myeloma (MM).

METHODSThe interphase fluorescence in situ hybridization (I-FISH) was performed on purified CD138⁺ plasma cells from 78 newly diagnosed patients from Sep 2007 to Sep 2012 receiving thalidomide-based chemotherapy by using BAC probe covered 1p21.2 region that contains the human cell division cycle 14A (HCDC14A) gene. Deletion rate, the cell percentage of deletion, clinical relevance and prognostic significance were analyzed in myeloma patients.

RESULTSAmong 78 patients, there were 51 males and 27 females, the median age was 59(42-81). The deletion rate of 1p21.2 was 23.1%. Some patients had amplification (amp) of 1p with amp rate of 5.1% in 1p21.2, the amp rate was significantly lower than the deletion rate (P=0.001). 1p21.2 deletion was positively correlated with renal lesion (Cr≥177 μmol/L), high percentage of plasma cells in bone marrow, high LDH (≥220 U/L) and high β2-MG (P=0.014, 0.000, 0.010 and 0.022, respectively). With a median follow-up time of 15.0(1.0-53.5) months, the estimated median progressionfree survival (PFS) and overall survival (OS) time for patients with 1p21 deletion was (12.0±2.7) and (14.0±3.4) months, however those were (30.0±8.0) and (38.5±1.8) months in patients without 1p21 deletion, respectively (P=0.000). On multivariate analysis, which included complex karyotype, LDH≥220 U/L, renal lesion and del(17p13), 1p21 deletion remained as an independent risk factor for PFS (HR: 3.312, 95% CI: 1.095-10.017, P=0.034) and OS (HR: 4.961, 95% CI: 1.487-16.552, P=0.009).

CONCLUSION1p21 deletion is an important genetic prognosis indicator in multiple myeloma patients.

Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Multiple Myeloma ; diagnosis ; drug therapy ; genetics ; Prognosis ; Thalidomide ; therapeutic use

This study was purpose to investigate the B7-H3 expression in multiple myeloma cell lines and CD138 cells of patients with multiple myeloma, and explore its clinical significance. Three myeloma cell lines (RPMI8226, U266 and H929) were used. Forty-five patients with multiple myeloma were enrolled in the study. The expression of B7-H3 was detected by flow cytometry and RT-PCR. The relationship between B7-H3 and clinical prognostic factor was analyzed. The results showed that (1)In myeloma cell lines, high expression of B7-H3 was seen in RPMI8226 (92.30 ± 1.1)% and U266 (79.03 ± 1.2)% but not in H929 cell line (4.26 ± 0.2)%. (2) Exogenous IL-6 had no effect on upregulation of B7-H3 in myeloma cell lines. (3) In multiple myeloma patients, the proportions of B7-H3 positive cells in newly diagnosed, remission and relapsed patients were (48.58 ± 33.593)%, (22.16 ± 18.853)%, and (57.65 ± 28.296)%, respectively. The difference between the newly diagnosed and remission patients, and remission and relapsed patients was significant (P = 0.023, P = 0.004). (4)High B7-H3 expression was correlated with high numbers of bone destruction and high levels of serum calcium (P = 0.027, P = 0.046, respectively). It is concluded that the relation of B7-H3 molecule expression with prognosis of multiple myeloma may be negative, but with degree of bone destruction is positive, thus the high expression of B7-H3 may correlated with disease progression and bone destruction of patients with multiple myeloma.
Adult ; Aged ; Aged, 80 and over ; B7 Antigens ; genetics ; metabolism ; Bone and Bones ; pathology ; Calcium ; blood ; Cell Line, Tumor ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; metabolism ; pathology ; Prognosis

BACKGROUND: We reviewed patients with multiple myeloma (MM) in order to assess the incidence of genetic abnormalities and their associations with clinical parameters, risk groups, and prognosis. METHODS: A total of 130 patients with MM were enrolled. The incidences of genetic abnormalities were determined in all patients. The relationships of the genetic abnormalities and clinical parameters were investigated. In addition, a survival analysis was performed. RESULTS: Abnormal karyotypes were detected in 42.3% (N=55) of the patients, and this was increased to 63.1% (N=82) after including the results determined with interphase FISH. Hypodiploidy was observed in 7.7% (N=10) of the patients, and all were included in the group with complex karyotypes (30.8%, N=40). The 14q32 rearrangements were detected in 29.2% (N=38) of the patients, and these most commonly included t(11;14), which was followed by t(4;14) and t(14;16) (16.2%, 11.5%, and 0.8%, respectively). Abnormal karyotypes and complex karyotypes were associated with disease progression markers, including low hemoglobin levels, low platelet counts, high plasma cell burden, high beta2-microglobulin, and high international staging system stages. A high free light chain (FLC) ratio and FLC difference were associated with abnormal karyotypes, complex karyotypes, and higher plasma cell burden. Hypodiploidy and low platelet counts were significant independent prognostic factors and were more important in patient outcome than any single abnormality. CONCLUSIONS: Genetic abnormalities were associated with disease progression markers and prognosis of MM patients.
Aged ; *Chromosome Aberrations ; Chromosomes, Human, Pair 14 ; Female ; Hemoglobins/analysis ; Humans ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/*genetics/mortality ; Neoplasm Staging ; Platelet Count ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Translocation, Genetic