P‐glycoprotein, lung resistance‐related protein and multidrug resistance associated protein in <i>de novo</i> acute non‐lymphocytic leukaemias: biological and clinical implications

Michieli, Mariagrazia; Damiani, D. Doḿınguez; Ermacora, Anna; Masolini, Paola; Raspadori, Donatella; Visani, Giuseppe; Scheper, R.J.; Baccarani, Michele

doi:10.1046/j.1365-2141.1999.01172.x

Cited by 108 publications

(83 citation statements)

References 34 publications

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“…[15][16][17][18][19][20] Expression of MDR1 in de novo AML patients is also associated with a poor outcome. [16][17][18][19]21,22,43 The MDR1 gene is localized on the long arm of chromosome 7 at band 7q21.1.…”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18][19][20] AML patients with −7/7q− have an extremely poor outcome, which is independent of the above mentioned clinical and immunological prognostic factors. [15][16][17][18][19][20][21][22] It is not known why and how the (partial) loss of a chromosome 7 affects the sensitivity of these AML cells to chemotherapy. [23][24][25] The breakpoint of partial chromosome 7 deletions is close to the 7q21.1 site of the MDR1 gene in many patients.…”

Section: Introductionmentioning

confidence: 99%

“…[12][13][14] In AML, MDR1 expression was identified as an independent adverse prognostic factor with respect to complete response to induction treatment and survival. [15][16][17][18][19][20][21][22] Also, other prognostic factors such as specific cytogenetic abnormalities, age, CD34 expression and white blood count at diagnosis have been identified. [15][16][17][18][19][20] AML patients with −7/7q− have an extremely poor outcome, which is independent of the above mentioned clinical and immunological prognostic factors.…”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19][20][21][22] Also, other prognostic factors such as specific cytogenetic abnormalities, age, CD34 expression and white blood count at diagnosis have been identified. [15][16][17][18][19][20] AML patients with −7/7q− have an extremely poor outcome, which is independent of the above mentioned clinical and immunological prognostic factors. [15][16][17][18][19][20][21][22] It is not known why and how the (partial) loss of a chromosome 7 affects the sensitivity of these AML cells to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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MDR1 expression in poor-risk acute myeloid leukemia with partial or complete monosomy 7

et al. 2001

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Expression of the multidrug resistance (MDR1) phenotype, encoded by the MDR1 gene, is an adverse prognostic factor for CR and survival in acute myeloid leukemia (AML). Other prognostic factors, such as specific cytogenetic abnormalities, have been identified in AML. We have investigated the expression of the MDR1 gene in untreated AML patients with monosomy 7 (n = 12), and partial deletions (n = 7) of the long arm of chromosome 7 (respectively −7/7q−), because of the extremely bad prognosis associated with these cytogenetic abnormalities and because of the fact that the MDR1 gene is located on chromosome 7q21.1.The findings were compared with the level of MDR1 expression in a group of 42 other AML patients, matched for age with favourable, neutral or complex cytogenetic abberations. MDR1 mRNA expression, as measured by the RNase protection assay was significantly higher in the −7/7q− group vs other AML patients (median 1.3 vs 0.1 arbitrary units, P = 0.02). Protein expression of MDR1 in the −7/7q− group, as determined with the monoclonal antibody MRK16, was found to be similar to the levels found in the control group. With a functional rhodamine retention assay using the modulator PSC833, increased MDR1 activity was observed in the −7/7q− group as compared to the control group of patients (P = 0.05). Considering the higher MDR1 mRNA expression and equal or slightly elevated level of protein expression of MDR1, we studied the presence of MDR1 genes in this group of −7/7q− patients. Fluorescence in situ hybridization (FISH) studies, using a specific MDR1 probe revealed no loss of an MDR1 allele in any of the deleted q− arms of the seven patients with 7q−, whereas all monosomy 7 patients lacked one MDR1 gene homologue. To determine whether there was selective loss of the MDR1 gene in the −7/7q− patients, the genetic polymorphism of the MDR1 gene was used. Both allelic variants (G and T) were represented in the −7/7q− and in the control group, showing a predominance for GT at position 2677 of the MDR1 gene in the control group. In the 12 monosomy 7 patients loss of the MDR1 allele was random. Methylation studies of the CpG island of the MDR1 gene revealed no hypermethylation in any of the −7/7q− patients. We conclude that MDR1 expression in −7/7q− AML patients is upregulated at transcriptional, but not at translational level, suggesting that mechanisms other than MDR1 are responsible for the poor prognosis in these patients. Leukemia (2001) 15, 398-405.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MDR1 expression in poor-risk acute myeloid leukemia with partial or complete monosomy 7

et al. 2001

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“…However, our findings are in contrast to other studies including the one of the Southwest Oncology Group in younger AML patients. 10,27,28 These discrepancies might be due to differences in patient populations both with regard to age and number of patients, treatment protocols, detection methods and other factors. 3 Our univariate findings on the predictive and prognostic significance of P-gp are consistent with previous reports.…”

Section: Figurementioning

confidence: 99%

Drug resistance factors in acute myeloid leukemia: a comparative analysis

et al. 2000

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To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0.008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.

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Antitumor Natural Products

Mitscher

Dutta

2003

Burger's Medicinal Chemistry and Drug Discovery

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The literature associated with major naturally occurring antitumor agents and related substances is reviewed and illustrated. Covered are dactinomycin, bleomycin, mitomycin, plicamycin, anthracyclines (daunorubicin, doxorubicin, epirubicin, idarubicin, and valrubicin), camptothecins (topotecan and irinotecan), idopodophyllotoxins (etoposide and teniposide), taxus diterpenes (docetaxel and paclitaxel), and vinca dimeric alkaloids (vinblastine, vincristine, and vinorelbine).

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P‐glycoprotein, lung resistance‐related protein and multidrug resistance associated protein in de novo acute non‐lymphocytic leukaemias: biological and clinical implications

Cited by 108 publications

References 34 publications

MDR1 expression in poor-risk acute myeloid leukemia with partial or complete monosomy 7

MDR1 expression in poor-risk acute myeloid leukemia with partial or complete monosomy 7

Drug resistance factors in acute myeloid leukemia: a comparative analysis

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