多发性骨髓瘤骨髓单个核细胞缺氧诱导因子1α mRNA的表达及其临床意义

目的 探讨多发性骨髓瘤(MM)患者缺氧诱导因子1 α(HIF-1 α)基因mRNA表达和临床各指标的相关性,了解HIF-1 α基因在MM患者中的表达和意义.方法 应用实时荧光定量聚合酶链反应(RQ-PCR)28例检测MM患者和22例骨科外伤患者或非血液系统恶性肿瘤患者(对照组)骨髓单个核细胞中的HIF-1 α mRNA,以β-actin作为内参照,用SDS分析软件测定Ct值,用2-△△Ct表示目的 基因的量.结果 HIF-1 α mRNA在MM骨髓单个核细胞中表达为对照组的12.68倍,HIF-1 α mRNA水平(以-△Ct表示)与患者血清β2-微球蛋白(r=0.575,P=0.000)、红细胞沉降率(r=0.522,P=0.000)、乳酸脱氢酶(r=0.286,P=0.044)、C反应蛋白(r=0.356,P=0.011)水平呈正相关,与患者血红蛋白(Hb)水平呈负相关(r=-0.556,P=0.000).结论 HIF-1 α mRNA在MM组织中高表达,与临床多项指标有关,可作为临床监测指标之一,有可能成为肿瘤分子靶向治疗中新的靶点.     

PTEN、MLL基因在T淋巴母细胞淋巴瘤/白血病的表达及其意义

目的 分析肿瘤抑制基因PTEN、混合系白血病(MLL)基因等在T淋巴母细胞淋巴瘤/白血病(T-LBL/ALL)的表达及意义.方法 选用76例T-LBL/ALl患者淋巴结存档蜡块,应用免疫组织化学EnVision法进行 PTEN标记,用20例反应性增生淋巴结标本作正常对照.并用荧光原位杂交(FISH)技术检测MLL基因所在1 1q23染色体的断裂和扩增情况.结果 76例T-LBL/ALL中,PTEN的表达率为64.47%(49/76),低于淋巴结反应性增生的100%(20/20)(λ2=19.220,P＜0.05).PTEN表达与临床分期、Ki-67、乳酸脱氢酶(LDH)呈负相关(P＜0.05).76例T-LBL/ALL中,MLL基因发生1 1q23染色体断裂13例(17.11%),扩增18例(23.68%).MLL基因断裂组总体生存率(25.0%)低于非断裂组(43.6%)(λ2=11.357,P＜0.05).MLL基因扩增组总体生存率(17.1%)低于非扩增组(42.7%)(λ2=4.533,P＜0.05).结论 抑癌基因PTEN表达降低在T-LBL/ALL的发生发展中可能具有重要作用.MLL基因发生染色体1 1q23断裂和扩增有助于对T-LBL/ALL预后的判断,发生MLL基因断裂或扩增的T-LBL/ALL预后较差,提示MLL基因断裂或扩增可能为T-LBL/ALL的一种分子亚型.     

应用LSI9q34探针及ES/DCDF探针检测慢性粒细胞白血病患者der(9)缺失的研究

目的 研究慢性粒细胞性白血病(CML)患者衍生9号染色体[der(9)]部分序列缺失情况,探讨LSI 9q34探针在检测der(9)缺失中的联合应用价值.方法 对52例CML患者采用不加任何刺激剂的骨髓进行24 h短期培养法制备染色体,吉姆萨显带进行核型分析.应用ES/DCDF探针及LSI 9q34探针对骨髓间期细胞进行荧光原位杂交,并检测der(9)部分序列缺失.结果 52例中经ES/DCDF探针检测全部为ber-abl融合基因阳性,其中12例患者伴有der(9)部分缺失,占23.0%,经LSI 9q34探针检测有11例患者伴有der(9)部分缺失.结论 LSI9q34探针在判断CML患者是否伴有der(9)缺失方面有较好的特异性.伴有缺失的患者疾病进展较快,预后较差,甲磺酸依马替尼治疗不能完全逆转其负性作用,建议所有bcr-abl融合基因阳性的CML患者均应行 LSI 9q34探针检测,以指导临床治疗.     

多发性骨髓瘤患者基质细胞衍生因子-1α、CD44v6表达的研究

目的 探讨基质细胞衍生因子-1α(SDF-1α)、CD44v6(一种变异的CD44受体)在多发性骨髓瘤(MM)中的表达水平及其与病情进展的关系.方法 用酶联免疫吸附试验(ELISA)检测24例MM患者[14例初发和复发MM患者(初发和复发MM组),10例病情稳定MM患者(病情稳定MM组)]和15位健康骨髓移植供者或非肿瘤良性贫血患者(对照组)的骨髓单个核细胞(MNC)和骨髓基质细胞(BMSC)培养上清的SDF-1 α、CD44v6水平.结果 初发和复发MM组MNC培养上清的SDF-1α、CD44v6表达水平[(7232.41±2644.97)pg/ml和(34.34±13.20)ng/ml]显著高于病情稳定MM组[(2315.49±748.29)pg/ml和(15.69±5.28)ng/m1](t=6.25、t=7.82;均P＜0.05)和对照组[(1149.52±636.06)pg/ml和(4.85±3.62)ng/ml](t=4.60、t=7.61;均P＜0.05).病情稳定MM组SDF-1α、CD44v6水平显著高于对照绀(t=2.99、t=4.87;均P＜0.05).9例初发和复发MM组的BMSC与人类骨髓瘤细胞系细胞U266加入rhIL-6进行混合培养后,SDF-1 α水平[(6180.25±5925.38)pg/ml]显著高于5例对照组BMSC[(1021.13±358.65)pg/ml]和9例初发和复发MM组[(1004.07±727.36)pg/ml](t=2.66、t=2.42;均P＜0.05).而其他BMSC各组问的SDF-1α水平差异无统计学意义(P＞0.05).SDF-1 α与CD44v6两者表达水平呈正相关(r=0.51,P=0.03).结论 SDF-1 α、CD44v6水平升高与MM的病情进展或发病有关,也可能与MM的肿瘤浸润过程有关;而这些体内过程可能需骨髓瘤细胞和BMSC与IL-6、SDF-1α和CD44v6等因素协同完成.     

急性髓系白血病细胞免疫表型与疾病复发的关系

目的 探讨急性髓系白血病(AML)细胞免疫表型与疾病复发的关系.方法 采用回顾性方法,对54例经标准化疗至少2个疗程达完全缓解的AML(非M3)患者的四色流式细胞术细胞免疫表型结果进行分析,评估22例复发AML患者发病时白血病细胞CD7、CD19、CD56、CD34、CD117、HLA-DR、CD11b、CD14、CD15、CD33、CD13的表达,同时与32例非复发AML患者的免疫表型进行对比.结果 22例复发患者AML抗原表达情况:CD7 27.3%,CD19 28.6%,CD56 81.8%,CD34 68.2%,CD117 90.0%,HLA-DR85.7%,CD11b 27.3%,CD14 14.3%,CD15 16.7%,CD33 95.5%,CD13 90.9%;32例非复发AML患者抗原表达情况:CD7 32.0%,CD19 8.0%,CD56 35.7%,CD34 64.0%,CD117 81.0%,HLA-DR91.3%,CD11b 43.5%,CD14 20.8%,CD15 28.6%.CD33 91.3%,CD13 92.0%;CD56表达与复发相关(RR=8.1,95%CI=1.2～53.2,P=0.021),其余各抗原与复发无相关性(P>0.05).结论 AML发病时白血病细胞CD56表达与疾病复发密切相关.     

硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺方案治疗多发性骨髓瘤

目的 观察硼替佐米联合异环磷酰胺、甲泼尼龙、沙利度胺(V-CMPT方案)治疗多发性骨髓瘤(MM)的临床疗效和患者不良反应.方法 回顾性分析应用V-CMPT方案进行治疗的24例初治和复发难治MM患者资料,3周为1个周期,治疗2个周期.应用骨髓细胞学检查、M蛋白鉴定以及其他血液学指标评价病情及疗效.结果 初治的9例患者中,完全缓解(CR)3例、部分缓解(PR)5例、轻微缓解(MR)1例;复发难治的15例患者中,CR2例、接近完全缓解(nCR)2例、PR 3例、MR 6例、无变化(NC)2例;两组间总缓解率(ORR)(P=0.511)及CR/nCR率(P=1.000)差异无统计学意义.总的CR/nCR率29.2%(7/24),ORR达到91.7%(22/24).2个周期V-CMPT化疗后,患者的血红蛋白、血清清蛋白及血清β2微球蛋白得到明显改善.不良反应包括胃肠道反应、血小板减少、周围神经病变等,经对症处理或间歇期停药多好转,不影响化疗的继续进行.结论 V-CMPT方案对初治和复发难治性MM临床疗效明显,能够明显改善血液学指标,药物耐受性良好.     

白血病Flt3基因编码的近膜区点突变的检测和内含子14缺失的分析

目的 对白血病Flt3基因编码的近膜区突变点进行检测,研究其与白血病发生、发展的关系.方法 应用聚合酶链反应(PCR)、聚合酶链反应单链构象多态性(PCR/SSCP)和DNA测序方法,对60例白血病患者外周血和部分骨髓标本Flt3基因外显子14、15进行检测.结果 在60例白血病患者中,3例白血病Flt3-L576P发生点突变,其中1例合并有Flt3基因内含子14缺失突变.结论 白血病Flt3-L567点突变是近膜区(JM)新发现的点突变,其发生与临床白血病的发生、发展具有相关性.     

新化合物Al14Gd5Si的晶体结构及其Rietveld精修

利用X射线粉末衍射技术和Rietveld结构修正方法对Al14Gd5Si进行了研究,新三元化合物Al14Gd5Si具有Ni3Sn结构类型,空间群为P63/mmc(No.194).点阵参数为a=0.63022 (1)nm,c=0.45856 (1)nm,指标化的可靠性因子F30=218.1(33).用Rietveld方法对该化合物的晶体结构成功地进行了精化修正,精修得到的R因子为Rp=0.119,Rwp=0.157.     

噬血细胞综合征患者血清血小板生成素水平的研究

目的 探讨血清血小板生成素(TPO)在噬血细胞综合征(HPS)患者中的表达水平及其临床意义.方法 收集2008年9月至2010年7月经首都医科大学附属北京友谊医院确诊的HPS患者26例,根据不同病因分为感染相关性HPS、肿瘤相关性HPS和风湿免疫病相关性HPS,同时收集26名健康人血清,分别采用酶联免疫吸附(ELISA)方法检测其血清TPO水平,并与各实验室检查指标进行相关性分析.结果 HPS患者组血清TPO水平显著低于健康对照组,差异有统计学意义(P=0.001),对HPS患者组中不同病因人群进行单因素方差分析,差异无统计学意义(P=0.183).检测HPS患者血清TPO水平与采血当日血小板、红细胞、血红蛋白、血肌酐、尿素氮、三酰甘油、纤维蛋白原、铁蛋白、NK细胞活性、sCD25水平的相关性,发现其与血肌酐水平呈正相关关系,与其他各项实验室指标均无相关性.结论 TPO可能与各种细胞因子一起影响了HPS患者血细胞的生成,TPO水平降低可能与HPS患者肝功能损害有关,其深层机制还有待进一步探讨.     

IHC与FISH检测乳腺癌HER2状态一致性的对比研究及其临床意义

目的:对比研究免疫组织化学方法(IHC)检测乳腺癌HER2蛋白表达和荧光原位杂交技术(FISH)检测HER2基因状态的一致性,并评价其临床意义.方法:采用IHC法及FISH法分别检测77例乳腺癌患者术后石蜡包埋标本的HER2蛋白表达和HER2基因状态,并进行对比分析.结果:77例乳腺癌患者术后石蜡包埋标本用IHC检测HER2蛋白表达阳性者37例,占总数的48.05%(37/77);表达阴性者40例,占51.95%(40/77).FISH检测HER2基因扩增32例,占41.56%(32/77);基因非扩增45例,占58.44%(45/77).37例HER2蛋白为阳性的患者中,HER2基因扩增30例,符合率为81.08%(30/37);40例HER2蛋白为阴性的患者中,HER2基因非扩增38例,符合率为95.00%(38/40).两种方法检测结果比较差异无统计学意义(χ2=1.78,P=0.1824).Kappa检验结果,κ=0.7647,表明一致性较好.结论:IHC检测乳腺癌HER2蛋白与FISH检测HER2基因结果一致性较高.     

Identification of new nonrandom translocations in multiple myeloma with multicolor spectral karyotyping

Multicolor spectral karyotyping (SKY) was performed on bone marrow samples from 50 patients with multiple myeloma (MM) in anticipation of discovering new previously unidentified translocations. All samples showed complex karyotypes with chromosome aberrations which, in most cases, were not fully characterized by G-banding. Patients of special interest were those who showed add(14)(q32), add(8)(q24) and those whose G-banding karyotypes showed poor chromosome morphology. Three new recurring chromosome translocations not previously reported in MM were identified. Two of the translocations involve recurring aberrations at band 14q32.3, the site of the IgH locus, with different exchange partners. The most frequently recurring rearrangement was a subtle translocation at 14q32.3 designated as a t(14;16)(q32;q22 approximately 23), which was identified in six patients. A second and larger translocation at 14q32, identified in two patients, was designated as a t(9;14)(p13;q32), previously associated with Waldenstrom's macroglobulinemia and lymphoplasmacytoid lymphoma. A third translocation, identified in two patients, involved a whole-arm t(6;8)(p10;q10) translocation. The SKY technique was able to refine the designations of over 156 aberrations not fully characterized by G-banding in this study and resolved additional chromosome aberrations in every patient studied except two. The t(14;16)(q32;q22 approximately 23) identified by SKY in this study suggests this may be a frequent translocation in MM associated with complex karyotypes and disease progression. Therefore, the SKY technique provides a useful adjunct to routine G-banding and fluorescence in situ hybridization studies in the cytogenetic analysis of MM.     

Characterization of t(11;14) translocation in mantle cell lymphoma by fluorescent in situ hybridization

Characterization of chromosome abnormalities in leukemia and lymphoma have contributed to the understanding of the molecular basis of these neoplastic diseases. In addition, specific chromosomal aberrations have acquired diagnostic or prognostic value. The t(11;14)(q13;q32) chromosome translocation has been detected in mantle cell lymphomas. However, possibly due to the limits of conventional cytogenetic analysis and the presence of different breakpoints at the molecular level, it is possible that the true percentage of association is underestimated. In our study, we used a yeast artificial chromosome, spanning the entire area where the rearrangements occur on chromosome 11q13, to detect the presence of translocations by fluorescent in situ hybridization experiments. We detected BCL-1 translocations in eight of eight patients with clinical and immunological features of mantle cell lymphoma, suggesting that the t(11;14) translocation is a critical event in the pathogenesis of MCL and may be a primary element for the diagnosis. Since this translocation is associated with poor prognosis, its detection may help to make a correct diagnosis as well as to evaluate residual disease, which is critical to plan a rational chemotherapy regimen.     

Multicolor spectral karyotyping identifies new recurring breakpoints and translocations in multiple myeloma

Karyotypic information on multiple myeloma (MM) is less extensive than that on other myeloid or lymphoid malignancies due to low mitotic activity of plasma cells. An add(14)(q32) marker chromosome has been reported to be the most frequent recurring abnormality in clonally abnormal cases; in approximately one third of the latter cases, this marker has been identified as a der(14)t(11;14)(q13;q32) chromosome. To map chromosomal breakpoints, characterize the add(14)(q32) marker chromosomes, and to identify other recurring translocations in MM, we used spectral karyotyping (SKY) to analyze a panel of nine bone marrow (BM) biopsy samples from eight patients and 10 tumor cell lines derived from MM patients. SKY involves hybridization of 24 fluorescently labeled chromosome painting probes to metaphase spreads in such a manner that simultaneous visualization of each of the chromosomes in a different color is accomplished. By this method, it was possible to define all chromosomal rearrangements and identify all of the clonal marker chromosomes in tumor cells. By detailed mapping of breakpoints of rearrangement, it was also possible to identify several novel recurring sites of breakage that map to the chromosomal bands 3q27, 17q24-25, and 20q11. The partner chromosomes in translocations that generated the add (14)(q32) marker chromosomes were identified in all cases in which they were detected by G-banding (one biopsy and six cell lines). In addition, two new translocations involving band 14q32, ie, t(12;14)(q24;q32) and t(14;20)(q32;q11) have also been identified. These studies demonstrate the power of SKY in resolving the full spectrum of chromosome abnormalities in tumors.     

High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies

Abnormalities involving the 14q32 region are recurrent chromosomal changes in plasma cell malignancies. Recent preliminary molecular analyses found IGH rearrangements in almost 100% of human myeloma cell lines and in 75% of patients. However, no systematic study analyzing the nature of the partner chromosomal regions have been reported thus far. To define the exact incidence of illegitimate IGH rearrangements and the respective incidence of partner genes cloned to date, we analyzed 141 patients with either multiple myeloma (MM, n = 127) or primary plasma cell leukemia (PCL, n = 14) using fluorescence in situ hybridization. The overall incidence of illegitimate recombinations was 57% (80 of 141 patients). Analysis of this incidence according to Durie and Salmon stage, patients' status, i.e., MM versus primary PCL and diagnosis versus relapse, immunoglobulin type and subtype, and beta2-microglobulin value, did not show any correlation. To analyze the nature of the partner chromosomal region, we selected probes specific for the following genes: FGFR3 (4p16), MYC (8q24), CCND1 (11q13), MAF (16q23), and BCL2 (18q21). These probes, combined with differentially labeled 14q32 probes, were used for dual-color fluorescence in situ hybridization on interphase plasma cells. Among the 80 patients with illegitimate IGH rearrangement, we identified 23 IGH-CCND1 fusion cases [i.e., t(11;14)], 17 IGH-FGFR3 fusion cases [i.e., t(4;14)], 3 IGH-MYC fusion cases [i.e., t(8;14)], and only one IGH-MAF fusion case. No IGH-BCL2 fusion case was detected. In 37 of 80 patients, none of these partner genes was involved. Analysis of cases with specific translocations according to their bioclinical features at diagnosis did not show any correlation. This study demonstrated that CCND1 and FGFR3 genes are involved together in about 50% of MM and primary PCL patients with illegitimate IGH rearrangements.     

Molecular analysis of 11q13 breakpoints in multiple myeloma

The t(11;14)(q13;q32) chromosomal translocation, which is the hallmark of mantle cell lymphoma (MCL), is found in approximately 30% of multiple myeloma (MM) tumors with a 14q32 translocation. Although the overexpression of cyclin D1 has been found to be correlated with MM cell lines carrying the t(11;14), rearrangements of the BCL-1/cyclin D1 regions frequently involved in MCL rarely occur in MM cell lines or primary tumors. To test whether specific 11q13 breakpoint clusters may occur in MM, we investigated a representative panel of primary tumors by means of Southern blot analysis using probes derived from MM-associated 11q13 breakpoints. To this end, we first cloned the breakpoints and respective germ-line regions from a primary tumor and the U266 cell line, as well as the germ-line region from the KMS-12 cell line. DNA from 50 primary tumors was tested using a large panel of probes, but a rearrangement was detected in only one case using the KMS-12 breakpoint probe. Our results confirm previous findings that the 11q13 breakpoints in MM are scattered throughout the 11q13 region encompassing the cyclin D1 gene, thus suggesting the absence of 11q13 breakpoint clusters in MM.     

Frequency and clinical significance of cytogenetic abnormalities in pediatric T-lineage acute lymphoblastic leukemia: a report from the Children's Cancer Group

PURPOSE: Nonrandom chromosomal translocations are frequently observed in pediatric patients with acute lymphoblastic leukemia (ALL). Specific translocations, such as t(4;11) and t(9;22), identify subgroups of B-lineage ALL patients who have an increased risk of treatment failure. The current study was conducted to determine the prognostic significance of chromosomal translocations in T-lineage ALL patients. MATERIALS AND METHODS: The study included 169 children with newly diagnosed T-lineage ALL enrolled between 1988 and 1995 on risk-adjusted protocols of the Children's Cancer Group (CCG) who had centrally reviewed cytogenetics data. Outcome analyses used standard life-table methods. RESULTS: Presenting features for the current cohort were similar to those of concurrently enrolled patients for whom cytogenetic data were not accepted on central review. The majority of patients (80.5%) were assigned to CCG protocols for high-risk ALL and 86.4% had pseudodiploid (n = 80) or normal diploid (n = 66) karyotypes; modal chromosome number was not a significant prognostic factor. Overall, 103 of 169 (61%) patients had an abnormal karyotype, including 31 with del(6q), 29 with 14q11 breakpoints, 15 with del(9p), 11 with trisomy 8, nine with 11q23 breakpoints, nine with 14q32 translocations, and eight with 7q32-q36 breakpoints. Thirteen patients had the specific 14q11 translocation t(11;14)(p13;q11) and all were classified as poor risk. Patients with any of these translocations had outcomes similar to those with normal diploid karyotypes. CONCLUSION: Chromosomal abnormalities, including specific nonrandom translocations, were frequently observed in a large group of children with T-lineage ALL, but were not significant prognostic factors for this cohort. Thus, contemporary intensive treatment programs result in favorable outcomes for the majority of T-lineage ALL patients, regardless of karyotypic abnormalities, and such features do not identify patients at higher risk for relapse.     

13q14 deletions are not primary events in B-cell chronic lymphocytic leukemia: a study of 100 patients using fluorescence in situ hybridization

Fluorescence in situ hybridization with a chromosome 12-specific alpha-centromeric probe and a 13q14 yeast artificial chromosome probe was performed on interphase cells from 100 patients with B-cell chronic lymphocytic leukemia. Thirty-one patients exhibited a 13q14 deletion. No correlation was found between 13q14 deletions and clinical stage, sex, or morphology. Sixteen patients had trisomy 12, including 6 (of 12) with an atypical morphology. Trisomy 12 and 13q14 abnormalities were detected concomitantly in three patients only. The analysis of patients with deletions clearly showed that in five cases a significant number of cells retained two signals with the yeast artificial chromosome probe, indicating a genetic heterogeneity among the leukemic population. Our data confirm that the 13q14 deletion is a frequent event, indicate that the concomitant occurrence of 13q14 deletion and trisomy 12 is rare but possible, and show that both abnormalities are secondary events in B-cell chronic lymphocytic leukemia.     

Oncogene rearrangement in non-Hodgkin's lymphoma with a 14q+ chromosome of unknown origin

Southern blot analysis was performed with a panel of DNA probes to detect rearrangements of c-myc, bcl-1, bcl-2 and bcl-3 in 14 cases of B-cell non-Hodgkin's lymphoma (NHL) with a clonal cytogenetic rearrangement involving the chromosome 14q32 locus and no known donor chromosome [t(14;?)(q32;?)]. In our experience, 21% of all chromosomal abnormalities involving the 14q32 locus in B-cell NHL are of this type. We found oncogene rearrangements in five of the 14 cases: bcl-1 rearrangement on one mantle zone lymphoma, bcl-2 rearrangements in two follicular lymphomas, and c-myc rearrangements in two small noncleaved cell lymphomas. We conclude that a 14q32+ abnormality of unknown origin is a relatively frequent karyotypic finding in B-cell NHL. In one third of the cases, known oncogenes that have been previously described in reciprocal translocations involving the immunoglobulin heavy chain locus were shown to be involved in the 14q32+ abnormality. The translocations in the other cases are likely to have involved one of the above oncogenes with breakpoints not revealed by the probes employed, other known oncogenes, or oncogenes that have not yet been identified.     

Expressed sequences as candidates for a novel tumor suppressor gene at band 13q14 in B-cell chronic lymphocytic leukemia and mantle cell lymphoma

Deletions affecting the interval between the RB1 gene and marker D13S25 at band 13q14 are the most frequent genetic abnormalities of B-cell chronic lymphocytic leukemia (B-CLL) and indicate the presence of a novel tumor suppressor gene in this region. In the current study, a high resolution physical map of fragments spanning one megabasepair (Mb) of genomic DNA at the critical 13q14 segment was constructed. To define the minimal region of loss within the RB1 and D13S25 interval, we screened 322 B-CLLs for deletions at either of the two loci. Thirty mantle cell lymphomas (MCLs) were included in the analysis because we observed a 13q14 deletion pattern similar to B-CLL in this disease. The incidence of 13q14 deletions was 51% in B-CLL and 70% in MCL, respectively. No frequent loss of the BRCA2 gene at band 13q12 was found. Detailed deletion mapping at band 13q14 with probes from the RB1-D13S25 interval lead to the identification of a critical deletion region 400 kb in size. Within this region two segments were most frequently affected, one at D13S272 120 kb in size and another 240 kb distal of D13S272 80 kb in size. From these two segments expressed sequences were identified as candidates for the putative 13q14 tumor suppressor gene involved in the pathogenesis of B-CLL and MCL.