Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression in acute leukemia

The prognostic significance of multidrug resistance (MDR) gene expression is controversial. We investigated whether multidrug resistance gene 1 (MDR1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA expression are associated with outcomes in acute leukemia patients. At diagnosis we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71 acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The expression of each of these genes was then expressed as a ratio in relation to beta-actin gene expression, and the three genes were categorized as being either 0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1% and 45.1 %, respectively. LRP mRNA expression was significantly associated with resistance to induction chemotherapy in acute leukemia patients, and in the AML proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively). Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr survival. The present data suggest that MDR expression affects complete remission and survival rates in acute leukemia patients. Thus, determination of MDR gene expression at diagnosis appears likely to provide useful prognostic information for acute leukemia patients.     

Multi-drug resistance (MDR1) gene expression in de novo acute leukemia cells: correlations with CD surface markers and treatment outcome.

One important mechanism of drug resistance in acute leukemia is the overexpression of the multi-drug resistance (MDR1) gene that encodes a 170-kDa membrane protein called P-glycoprotein. To estimate the incidence and role of MDR1 gene expression in patients with acute leukemia, we investigated the expression of MDR1 by using the RT-PCR method in blast cells from 40 cases of de novo acute leukemia. We found a high frequency of MDR1 gene expression: 10 out of 20 with de novo acute myeloid leukemia (AML), 8 out of 17 with de novo acute lymphoblastic leukemia (ALL), and none of the 3 with de novo acute mixed leukemia, were MDR1 mRNA-positive. No correlation between cluster designation (CD) surface markers (CD19, CD7, CD13, CD33, CD34, CD14, HLA-DR) and MDR1 gene expression in AML was found. The complete remission rate was correlated with MDR1 gene expression. Among 40 evaluable patients examined, 17% (3 of 18) with MDR1 mRNA-positive reached complete remission versus 77% (17 of 22) with MDR1 mRNA-negative (p=0.044). These results suggest that MDR1 gene expression can be used as a prognostic factor and may be helpful in determining chemotherapeutic protocol for patients with acute leukemia.     

Association between multidrug resistance-associated protein 1 and poor prognosis in patients with nasopharyngeal carcinoma treated with radiotherapy and concurrent chemotherapy

ATP-binding cassette (ABC) multidrug transporters have been associated with chemoresistance, which is a major obstacle in attempts to improve clinical outcome of patients with nasopharyngeal carcinoma (NPC). In this study, we investigated 3 ABC multidrug transporters including MDR1, MRP1, and BCRP for their potential as prognostic indicators in patients with NPC. We examined the protein expression profiles of MDR1, MRP1, and BCRP in NPC tissues from 60 patients with advanced stages who were treated with radiotherapy and concurrent chemotherapy. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the transporter expression. Univariate analyses were performed to determine the prognostic factors that influenced treatment failure and patient survival. We found that MRP1 expression was strongly predictive of both 5-year survival (P = .025) and disease-free survival (P < .001). However, neither MDR1 nor BCRP expression was correlated with the clinicopathologic parameters. Interestingly, the incidence of recurrence and metastasis for patients in the MRP1-positive group was significantly higher than that in the MRP1-negative group (P = .003). With multivariate analysis, MRP1 expression at the time of diagnosis before the treatment was identified as an independent prognostic factor for both 5-year survival (P = .041) and disease-free survival (P = .001). MRP1 expression can therefore be used as a potent molecular risk factor and a guide for chemotherapeutic regimens in patients with advanced stages of NPC.     

Plasma soluble interleukin-2 receptor (sIL-2R) levels in patients with acute leukemia

The plasma soluble interleukin-2 receptor (sIL-2R) level was higher in 137 patients with acute leukemia (1,489 +/- 1,798 U/ml, including 98 cases of acute myeloid leukemia (AML), 1,063 +/- 1,414 U/ml, and 39 cases of acute lymphoblastic leukemia (ALL), 2,561 +/- 2,194 U/ml), compared to 49 normal control subjects, 421 +/- 151 U/ml). The ALL patients showed elevated plasma sIL-2R levels more frequently than the AML patients (92.3% vs 44.9%). No patient with either hypoplastic AML or AML with multilineage dysplasia and only 1 of 13 patients with acute promyelocytic leukemia (APL) had an elevated plasma sIL-2R level. All the My+ ALL patients (15 cases) showed elevated plasma sIL-2R levels. Plasma sIL-2R levels were significantly lower after chemotherapy in the ALL patients, but were not significantly lower in the AML patients. IL-2R was expressed on the leukemic cells in 36 (53.7%) of 67 AML and in 9 (21.4%) of 42 ALL cases. None of the AML M3, M4, M5, M6, or M7 subgroups showed IL-2R expression. The My+ ALL patients (42.9%, 6/14) showed IL-2R expression more frequently than the other ALL subgroups (10.7%, 3/28) (p = 0.025). The plasma sIL-2R level was correlated with the proportion of leukemic cells expressing IL-2R in acute leukemia. However, there were many cases, particularly ALL cases, who had elevated plasma sIL-2R levels without IL-2R expression on their leukemic cells. These results suggest that the plasma sIL-2R level is a valuable marker for monitoring ALL after chemotherapy, particularly in My+ ALL cases, and that the T cell immune reaction to leukemia appears to be much higher in ALL patients than in AML patients.     

Gene polymorphisms of ABC transporters are associated with clinical outcomes in children with acute lymphoblastic leukemia

Introduction

Genetic variability affects clinical outcome in pediatric acute lymphocytic leukemia (ALL) patients. Evaluating gene polymorphisms in ABC transporters could help identify relapse risk and predict outcome.

Material and methods

The SNaPshot SNP technique was used to analyze single-nucleotide polymorphisms (SNPs) in the multidrug transporter 1 (MDR1), multidrug resistance associated proteins (MRP1, MRP2) and breast cancer resistance protein (BCRP) genes of 82 pediatric ALL patients. The association between the SNPs with risk of all events and death as well as with survival was evaluated by the univariate Cox proportional hazard model.

Results

The BCRP G34A SNP was the only SNP significantly associated with ALL. Risk factors included pre-treatment WBC counts and post-treatment peripheral and bone marrow leukemic cell counts. We found no association between MDR1 SNPs with these factors. The BCRP C421A C/A and C/C genotypes were significantly associated with low pre-treatment WBC counts while MRP2 G1249A G/G was significantly associated with low levels of post-treatment peripheral and bone marrow leukemic cells. A combination of C1236T, G1249A and/or G34A SNPs was significantly associated with lower EFS and OS.

Conclusions

Polymorphisms associated with risk of ALL and clinical outcome may be potential biomarkers to predict clinical outcome and improve prognosis in childhood ALL.     

Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients

The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1–2 years postoperatively. Adenosine triphosphate (ATP)‐binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR‐associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35 (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases, respectively. The expression statuses of the MDR‐related proteins were positively correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2 (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion. MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047). High BCRP expression in PDAC was a significant prognostic factor for early tumor recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR‐related proteins are frequently expressed in PDAC, and high BCRP expression is a significant independent predictor for early recurrence and poor survival. Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in identifying a subgroup of patients with a poor prognosis.     

Expression dynamics of drug resistance genes, multidrug resistance 1 (MDR1) and lung resistance protein (LRP) during the evolution of overt leukemia in myelodysplastic syndromes

It is well-known that leukemic cells of overt leukemia (OL) that have transformed from myelodysplastic syndromes (MDS) are more resistant to chemotherapy as compared with de novo AML cells. Thus, to examine the expression levels of drug-resistant genes and their alterations with the development of OL in MDS, the expression of mRNA for MDR1 and LRP was determined in bone marrow samples from control, de novo AML, MDS, MDS at the time of OL transformation (MDS --> OL), and after transformation (OL) by quantitative real-time RT-PCR. The expression of MDR1 in MDS bone marrow at the time of initial diagnosis was as low as that for control subjects. However, the expression level was significantly elevated at the time of the development of OL (MDS --> OL) compared with the initial MDS subjects (P < 0.05), while expression was relatively reduced after OL development (OL). The expression of LRP was significantly higher in MDS and MDS --> OL samples than control subjects. However, the high expression of LRP in MDS --> OL was significantly reduced after OL development (OL). The expression levels of drug-resistant genes in MDS --> OL or OL were not significantly higher than those of de novo AML samples, although LRP expression in MDS or MDS --> OL was relatively higher than that of de novo AML. Detecting increases in the expression of MDR1 would be useful for predicting OL development in MDS patients.     

Immunohistochemical expression of multidrug resistance proteins in mature T/NK‐cell lymphomas

Multidrug resistance (MDR) is defined as resistance of tumor cells to a wide spectrum of structurally and functionally unrelated drugs. One of the most important mechanisms in mediating MDR is that involving cellular drug efflux transporters. Drug resistance is a common and formidable obstacle to therapy in mature T/NK‐cell lymphomas and the MDR phenotype is thought to be one of the contributing mechanisms. In this study we assessed the immunohistochemical expression of P‐gp (P‐glycoprotein), MRP‐1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) in 45 mature T/NK‐cell lymphomas diagnosed at our hospital. We detected P‐gp expression in 31% (13/42), MRP‐1 expression in 74% (31/42), BCRP in 78% (32/ 41) and LRP in 59% (26/44) of the cases. These findings show that our T/NK‐cell lymphoma cases display high frequency of MDR protein expression.     

Acute myeloid and lymphoblastic leukemia in adults. The course of the disease in 315 patients from one region, during a ten-year period

In a ten-year retrospective singlecenter study of a nonselected patient population, we describe our experience with an unchanged chemotherapy regimen for 264 patients with acute myeloid leukemia (AML) and 51 patients with acute lymphoblastic leukemia (ALL). In the AML group, 85 patients could not receive specific antileukemic treatment because of uncontrollable bleeding, infection or organ failure, but 179 were fit for remission-induction therapy with cytarabine and daunorubicin, resulting in complete remission in 79 patients. During treatment, 54 patients died of resistant disease or complications. The median duration of survival of the patients in complete remission was 18-24 months (n = 79) compared with 1-2 months for patients in partial or no remission (n = 100). As maintenance chemotherapy, thioguanine, cytarabine and daunorubicin were given for one year. In the ALL group 50 of 51 patients received remission-induction therapy with vincristine, prednisone and Adriablastin, resulting in complete remission in 39 of the patients. The median duration of survival of the patients in complete remission was nine months (n = 39) compared with 2-3 months for patients not in remission (n = 12). Central nervous system prophylaxis with intraspinal methotrexate and cranial irradiation was given, followed by methotrexate and Purinetol for three years as maintenance chemotherapy. The remission rate for AML and adult ALL was 44% and 78%, respectively. The major Cause of death after first complete remission was leukemic relapse in boths groups, with a median survival time after relapse of 3-4 months for 48 AML and six months for 30 ALL patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Erythropoietic activities in acute leukemia and in malignant lymphoma with or without bone marrow involvement

Erythropoietic activities and immature reticulocyte production were investigated in a total of 157 patients (81 men, 76 women, median age = 42 yr, range = 23 to 65 yr) with acute lymphoid leukemia (ALL, n = 31), acute myeloid leukemia (AML, n = 39), or non-Hodgkin's lymphoma (NHL, n = 87), based on assays of the hemogram, red cell indices, reticulocyte subpopulations, and intramedullary erythroid precursors. There were no significant differences in red blood cell (RBC) counts, blood hemoglobin levels, or erythroid precursors between ALL and AML patients. Reticulocytes in AML patients averaged 1.7 +/- 0.8%, which was higher than in patients with ALL (0.8 +/- 0.3%, p <0.01); the proportion of high-fluorescence reticulocytes (HFR) averaged 4-fold higher in AML versus ALL (p <0.01) and the reticulocyte maturity index (RMI) was higher in AML (20.8 +/- 8.3%) versus ALL (12.4 +/- 6.5%, p <0.01). The RMI was higher in NHL patients with bone marrow (BM) involvement (15.6 +/- 9.4%), compared to those without BM involvement (4.3 +/- 2.1%, p <0.01). The proportion of HFR averaged 11-fold higher in NHL with BM involvement versus NHL without BM involvement. In summary, erythropoietic activity is significantly more active in patients with AML compared to ALL and in patients with NHL with BM involvement, compared to NHL without BM involvement.     

ABC转运蛋白基因多态性与晚期非小细胞肺癌铂类药物化疗的相关性

目的：研究ABC转运蛋白基因多态性与晚期含铂方案化疗的非小细胞肺癌(non-small cell lung cancer, NSCLC)患者化疗敏感性和耐受性的关系。方法：经病理学确诊的III/IV期NSCLC患者240例,采用顺铂或卡铂为主的方案进行化疗,2个周期后进行临床疗效和毒副反应评价。用MASS-ARRAY的方法进行MDR1 C3435T、MDR1 C1236T、BCRP C421A、MRP2 I1324I和MRP2?24C>T多态性的分型。用SPSS软件分析不同基因型与化疗敏感性和毒副反应的相关性。比值比(odds ratios,OR)及95% CI以logistic回归模型计算。结果：MRP2?24C>T C/T型客观缓解率(objective response rate, ORR)显著降低(P=0.026,OR=3.036,95% CI：1.143~8.061);MRP2 I1324I A/G型更容易出现血小板减少P=0.028,OR=6.829,95% CI：1.232~37.869);MRP2?24C>T C/T型更容易出现血小板减少(P=0.029,OR=6.592,95% CI：1.217~35.695)。结论：MRP2 I1324I、MRP2?24C>T多态性可以预测非小细胞肺癌患者对含铂方案化疗的缓解率和骨髓抑制情况。     

Impact of cellular CD71 (transferrin receptor 1) expression in Egyptian acute leukemia: correlation with clinicopathologic features

Cellular transferrin receptor 1 (CD71) has been identified as a proliferation marker. Inferior outcome with higher expression was observed in many solid tumors. This study objected to assess the expression of CD71 in patients with acute leukemia and to address its prognostic significance and relations to clinicopathologic features. The study included 34 acute myeloid leukemia (AML) and 64 acute lymphoblastic leukemia (ALL) newly diagnosed cases from Mansoura Oncology Center. CD71 was analyzed on blast cells by flow cytometry. CD71 expression was significantly elevated in both AML and ALL. Antigen expression apparently increased in T-ALL, while in AML there was a trend toward a gradual increase of antigen expression in relation to maturation evidence of myeloid subtypes. CD71 expression correlated positively with total leukocyte count in ALL cases and negatively with platelet count in AML cases. In ALL, higher CD71 expression was associated with higher relapse rate and was an independent prognostic factor of overall survival (HR 1.8; 95 % CI 1.2–4.1). In conclusion, CD71 is overexpressed in acute leukemia; it predicts adverse clinical outcome in ALL. In addition, CD71 antagonism could be a possible therapeutic target in acute leukemia.     

High order interactions of xenobiotic metabolizing genes and P53 codon 72 polymorphisms in acute leukemia

Polymorphisms in xenobiotic metabolizing genes are associated with altered metabolism of carcinogens in acute leukemia (AL). This study applied two data mining approaches to explore potential interactions among P53 and xenobiotic metabolizing genes in 230 AL patients [131 acute myeloid leukemia (AML) and 99 acute lymphoblastic leukemia (ALL)] and 199 controls. Individually, none of the genotypes showed significant associations with AML risk. However, in ALL the CYP1A12A TC genotype was associated with increased risk (OR = 2.02; 95% CI = 1.14–3.58; P = 0.01), whereas the GSTM1 null genotype imparted reduced risk (OR = 0.55; 95% CI = 0.31–0.96; P = 0.03). In classification and regression tree analysis, combinations of GSTM1 present, CYP1A12C AA or GG, EPHX1 exon3 TC, and EPHX1 exon4 AA or GG genotype strongly enhanced the risk of AML (OR = 5.89; 95% CI = 1.40–26.62; P = 0.01). In ALL, combinations of CYP1A12A TT, P53 GG or CC and GSTP1 AG genotypes conferred the highest risk (OR = 4.19; 95% CI = 1.45–12.25; P = 0.004). In multifactor dimensionality reduction analysis, a four locus model (GSTP1, P53, EPHX1 exon3, and CYP1A12A) was the best predictor model for ALL risk. The association between this model and ALL risk remained true even at low prior probabilities of 0.01% (false positive report probability = 0.05). Interaction entropy interpretations of the best model of ALL revealed that two‐way interactions were mostly synergistic. These results suggest that high order gene–gene interactions play an important role in AL risk. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

乳腺癌新辅助化疗对耐药基因MDR1和MRP表达的影响

目的:探讨乳腺癌新辅助化疗对耐药基因MDR1和MRP表达的影响。方法:采用半定量RT-PCR方法检测20例乳腺癌病人新辅助化疗前、后肿瘤组织中耐药基因MDR1和MRP的表达情况,并采用自身对照研究新辅助化疗对耐药性的影响。结果:化疗前20例乳腺癌组织中有15例(75%)MDR1表达,18例(90%)MRP表达。化疗后,经自身对照检测发现,MDR1的表达无显著差异,而MRP的表达与化疗前相比有显著差异。结论:在乳腺癌中新辅助化疗对耐药基因MDR1的表达无影响,但可增加MRP的表达.     

可溶性B7-H3(sB7-H3)在急性白血病中的检测及临床意义

目的:检测sB7-H3在急性白血病病人脑脊液中的不同表达,以及分析该分子的表达与急性白血病的亚型的相关性。方法:采用ELISA的方法来检测sB7-H3在176位白血病病人脑脊液中的表达。依据国际公认的FAB(French-Amer-ican-British)分类系统将急性白血病病人分型。结果:sB7-H3在急性淋系白血病与急性髓系白血病中的表达差异显著(P=0.0381),这与人白血病细胞株的检测结果一致;在急性淋系白血病的亚型中,sB7-H3的表达没有显著性差异;在急性髓系白血病的亚型中,sB7-H3的表达在M3与M5和M4与M5之间存在显著性差异(分别为P=0.024 3和P=0.022 3)。结论:sB7-H3的表达与白血病的分型具有一定的相关性,同时也进一步证实B7-H3参与了人体免疫平衡的调节,可能会为今后急性白血病的临床诊断提供依据。     

Early stem cell transplantation for refractory acute leukemia after salvage therapy with high-dose etoposide and cyclophosphamide.

Primary refractory acute leukemia (AL) has a poor prognosis, although some patients can be salvaged with allogeneic stem cell transplantation (SCT). Induction of complete remission (CR) with conventional chemotherapy before SCT may improve outcome in this patient population. Between March 1991 and October 2003, 59 adults with primary refractory AL were treated with continuous-infusion etoposide (VP) 2.4 to 3.0 g/m(2) followed by cyclophosphamide (Cy) 6.0-7.2 g/m(2) intravenously over 3 to 4 days with the intention of proceeding to SCT in CR1. Forty-two patients had acute myelogenous leukemia (AML), 13 patients had acute lymphoblastic leukemia (ALL), and 4 patients had acute biphenotypic leukemia. The most frequent nonhematologic toxicities were oral mucosal, gastrointestinal, and hepatic toxicities (44%, 20%, and 15% of patients, respectively). Thirty-two (57%) of 56 evaluable patients entered CR1 with a median time to platelet and neutrophil recovery of 22 and 26 days, respectively. CR1 rates were similar in AML (54%) and ALL/acute biphenotypic leukemia (67%; P = .52), and analysis of baseline characteristics did not reveal any predictors of response to VP/Cy. Twenty-nine of 32 CR1 patients subsequently underwent SCT (24 allogeneic and 5 autologous). Estimated 5-year event-free survival (EFS) and overall survival for the entire cohort are 23% and 26%, respectively. In the allogeneic SCT group, 5-year EFS was 52% for AML patients and 14% for ALL patients (P = .04), and only male sex was predictive of a favorable outcome (P = .03). VP/Cy is able to induce CR1 in most patients with primary refractory AL with an acceptable toxicity profile. Subsequent allogeneic SCT can lead to long-term EFS in a significant proportion of patients.     

The proportion of abnormal karyotypes in acute leukemia samples related to method of preparation

Bone marrow and peripheral blood were studied from 200 patients with acute leukemia [109 with acute myeloid leukemia (AML), 91 with acute lymphoblastic leukemia (ALL)] who had samples cultured for varying times and who had a mixture of chromosomally abnormal and normal cells. The mean percentage of abnormal metaphase cells increased with culture time. The peak was reached at 48 hours and declined slightly after 72 hours in culture for ALL patients. The mean percentage of abnormal cells increased up to 72 hours in culture for AML patients. In 68 patients (31 AML and 37 ALL), cytogenetic data were available from samples processed with both direct preparations and culture methods. The percentage of abnormal cells increased after culture in 49 patients (23 AML and 26 ALL), while it decreased or remained at the same level in 19 patients. For AML patients, the mean percentage of abnormal cells was significantly different between direct (38%) and cultured preparations (63%), (p less than 0.001). Seven of 9 patients with AML who showed a greater than 50% increase in abnormal cells after culture had either a t(8;21), t(15;17), or abnormalities involving 11q23. The two patients who showed a significant decrease in abnormal cells both had a translocation involving 11q13. Compared with ALL, more AML patients showed greater than 80% abnormal bone marrow metaphase cells at diagnosis or at relapse.     

原发性肝癌粘附分子基因的表达与化疗敏感的相关性研究

目的：探讨原发性肝癌粘附因子基因的表达与化疗敏感的相关性。方法： 取64例肝癌切除组织行ATP-TCA法肿瘤体外药敏试验，以RT-PCR法半定量检测肝癌多种粘附因子、多药耐药基因表达情况。 结果： 肝癌组织E-cadherin, ICAM-1, CD44, CD44V, α5,β1基因mRNA的表达量分别为1.24±0.54, 0.96±0.37, 0.62±0.73, 0.86±0.33, 0.97±0.49, 1.41±0.24，其中CD44与E-cadherin、β1的表达量有显著差异。多药耐药基因MDR1、MRP、GST-π、LRP、TOPOⅡ的表达量分别为1.17±0.47、1.59±0.33、1.18±0.48、1.03±0.48、1.00±0.31。各粘附分子基因的表达与多药耐药基因的表达有一定的相关性：其中ICAM-1、α5的表达与MDR1的表达呈正相关，E-cadherin、CD44的表达与MDR1的表达呈负相关； E-cadherin的表达与MRP的表达呈负相关；ICAM-1的表达与LRP的表达呈正相关，E-钙粘连素、CD44的表达与LRP的表达呈负相关。肝癌化疗疗效与粘附分子基因mRNA表达量的关系：在化疗有效组E-cadherin、CD44的mRNA表达量高于无效组，ICAM-1、CD44V、α5、β1的mRNA表达量低于无效组。两组差别无显著意义。结论： 在肝癌部分粘附分子的基因mRNA的表达与部分多药耐药基因mRNA的表达相关，与化疗的疗效有关。     

MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with Fanconi anemia

We describe a boy with Fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. Genes Chromosomes Cancer 27:264-269, 2000.