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MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is characterized by complex genetic and chromosomal abnormalities involving both numerical and structural aberrations, which have clinical prognostic value. The plasma cell labeling index (PCLI) is one of the most important prognostic factors in newly diagnosed MM, and indicates plasma cell proliferative capacity. In this study, we determined the PCLI and the deletion of 13q14, retinoblastoma-1 gene (RB-1), 1p13, and 17p13, 1q21 amplification, and IgH rearrangements in 42 newly diagnosed patients with MM. A high PCLI was observed in 18 patients (42.9%%), and the del(13q14) was present in 25 patients (59.5%%), del(RB-1) in 23 patients (54.8%%), del(17p13) in eight patients (19.1%%), amp(1q21) in 23 patients (54.7%%), del(1p13) in 17 patients (40.5%%), and IgH rearrangements in 28 patients (66.7%%). We further detected the IgH translocation partners: t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23) in 19, 15, and five patients, respectively. The PCLI had a significant correlation with del(13q14) ( p == 0.006), but no correlation with other chromosome abnormalities or clinical and laboratory features ( p > 0.05). The PCLI was higher among patients with del(13q14), and patients with a high PCLI had a short time to disease progression. In conclusion, PCLI is a powerful and independent prognostic parameter in newly diagnosed MM, and correlates with del(13q14). [ABSTRACT FROM AUTHOR]

Objective: To detect chromosomal aberrations by using cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH), and to explore the correlation of del(17p13) with clinical characteristics, drug response and prognosis among patients with newly diagnosed multiple myeloma (NDMM)., Methods: Clinical data of 198 cases of NDMM was collected. cIg-FISH and a specific probe (TP53) were used to detect karyotypic abnormalities in bone marrow samples derived from the patients. Correlation between karyotypic abnormalities and clinical data was analyzed., Results: Nineteen of the 198 patients (9.6%) were found to have a karyotype involving del(17p13). The overall survival (OS) and progression-free survival (PFS) for patients with or without del(17p13) was significantly different (P<0.01). No significant difference was found in OS and PFS between patients carrying a del(17p13) on bortezomib and non-bortezomib regimen (OS: P = 0.873; PFS: P = 0.610)., Conclusion: cIg-FISH is a simple and convenient method for the detection of karyotypic anomalies in multiple myeloma. Del(17p13) is an indicator for poor prognosis for multiple myeloma patients. Bortezomib cannot improve the survival disadvantage of del(17p13).

The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05). Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib-based regimens.

MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP)-dependent efflux transporter that plays a fundamental role in transportation of harmful compounds outside cells to maintain optimal health. The present study was aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A, and C3435T were focused on, and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele-specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6 vs. 60.0 %, respectively; hazard ratio (HR) = 0.1, 95 % confidence interval (CI) 0.01-0.6, p = 0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7 vs. 51.9 %, respectively; p = 0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4 % in with T group vs. 73.7 % in without T group, respectively; HR = 1.9, 95 % CI 1.0-3.6, p = 0.045). At locus G2677T/A, the age for genotypes AG and AT groups was significantly younger than the other genotypes (51.1 ± 12.6 vs. 57.7 ± 13.4 years, respectively; p = 0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0 vs. 50.6 %, respectively; HR = 7.8, 95 % CI 1.9-32.6, p = 0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT + TT at locus C1236T, allele C, and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL.

T(12;14)(p13;q32) is a rare recurrent chromosomal translocation, which has only been identified in a small subgroup of mantle cell lymphoma (MCL) without typical t(11;14)(q13;q32). This rearrangement causes aberrant over-expression of cyclin D2 (CCND2), which disrupts the normal cell cycle. Here we report a subtle case of MCL with t(12;14)(p13;q32) that was initially misdiagnosed as ultra-high risk chronic lymphocytic leukemia (CLL). A 60-year-old male patient presented with obvious leukocytosis and progressive weakness. Morphology of peripheral blood and immunophenotyping by flow cytometry pointed to a diagnosis of chronic lymphocytic leukemia. Fluorescence in situ hybridization (FISH) using IGH-CCND1 probe was negative for CCND1 abnormality, but demonstrated IGH breakapart signals. The initial diagnosis of CLL was established and the patient was treated with six courses of immunochemotherpy with fludarabine, cyclophosphamide and rituximab (FCR). Complete remission (CR) was achieved at the end of treatment, but disease relapsed quickly. The patient was transferred to our hospital, flow cytometry using additional markers showed that the clonal cells were CD200+(dim), CD148+(strong), and chromosome analysis revealed a complex karyotype, 47, XY, t(12;14)(p13;q32), +12, del(9p21), which indicated over-expression of CCND2, and immunostaining showed strong positivity of SOX11 further confirming the characteristics of CCND1-negtive MCL. The final diagnosis was revised to rare subtype of MCL with CCND2 translocation and intensive regimens were employed. This confusable MCL case illustrates the importance of cytogenetic analysis and clinicopathologic diagnosis of this rare category of MCL.

Objective: To investigate the characteristics of the abnormalities of chromosome 17 in myeloid malignancies with complex chromosomal abnormalities (CCAs)., Methods: Abnormalities of chromosome 17 were analyzed in 73 patients with myeloid malignancies with CCAs showed by R banding and conventional karyotyping, including 21 acute myeloid leukemia (AML), 36 chronic myeloid leukemia (CML) and 16 myelodysplastic syndrome (MDS). All CCAs were further analyzed by multiplex fluorescence in situ hybridization (M-FISH)., Results: Among the 73 myeloid malignancies with CCAs, chromosome 17 was the most frequently involved chromosome. It was found in 46.5% (34/73) of all cases, including 12 AML, 13 CML in blast crisis (BC) and 9 MDS. However, it was not found in the 9 CML cases in chronic phase (CP). The majority of changes were structural rearrangements which were identified in 43.8%(32/73)of all cases, among them the frequency was 52.4% (11/21), 33.3% (12/36) and 56.3% (9/16) in AML, CML and MDS, respectively. Numerical abnormalities were detected in 15.1% (11/73) cases, all were monosomy 17, and the frequency was 25.0% (3/12), 38.5% (5/13) and 33.3% (3/9) in AML, CML and MDS, respectively. Both numerical and structural abnormalities of chromosome 17 were found in 9 cases. Unbalanced translocations involving chromosome 17 were much more frequent than balanced ones. In the 3 groups, 16, 15 and 8 unbalanced translocations were found respectively. Only two kind of balanced translocations including t(15;17) in AML and t(15;17;22) in CML were found. All chromosomes were involved except chromosomes 5, 6 and 22 as partner chromosomes, the most common one was chromosome 15 (8.2%), followed by chromosome 2 (5.4%). Five of the 6 cases with translocation of chromosomes 15 and 17 were acute promyelocytic leukemia, the other case was CML-BC., Conclusion: Abnormalities of chromosome 17 were the most frequently involved chromosomal aberrations in myeloid malignancies, and structural rearrangements were more common. All the numerical abnormalities were monosomy 17, unbalanced translocations were much more frequent than balanced ones.

Objective: To evaluate the incidence of chromosomal abnormalities in Burkitt leukemia (BL)., Methods: Conventional cytogenetics (CC) was carried out to detect the karyotypes. Meanwhile, three color interphase fluorescence in situ hybridization (FISH) was used to detect the t(8;14)(q24;q32) in 17 newly diagnosed BL., Results: The results showed that the incidence of chromosomal abnormalities was 41.2% (7/17) by CC technique, including one of each for simple t(8;14)(q24;q32), complex chromosomal abnormality containing t(8;14)(q24;q32), t(8;22)(q24;q11), the complex chromosomal abnormality of t(12;22)(?;?), t(2;13)(?;?) with + 12, and one with two marker chromosomes. FISH method detected eight cases of t(8;14)(q24;q32), including the two detected by CC technique. Five samples (5/8) showed 2A1G1O2F (two blue, one green, one orange and two yellow signals in interphase nuclei), while three samples (3/8) showed 2A1G1O1F(two blue, one green, one orange and one yellow signals in interphase nuclei)., Conclusion: Two different breakpoints have been identified on the c-Myc locus on 8q24. Interphase FISH was more sensitive in detecting t(8;14)(q24;q32), and it is an important complement to CC. It should be used as a routine method for diagnosis of BL.