Contrary to adult patients, expression of the multidrug resistance gene (MDR1) fails to define a poor prognostic group in childhood AML

Steinbach, Daniel; Furchtbar, S; Sell, Wieland; Lengemann, Janka; Hermann, J; Zintl, F; Sauerbrey, Axel

doi:10.1038/sj.leu.2402806

Cited by 29 publications

(15 citation statements)

References 7 publications

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“…Similarly, and likewise contrary to adults, expression of the multidrug resistance gene (MRD1) failed to define a poor-prognostic group in childhood AML. 20 However, the prognostic value of cytogenetics is well established in all age groups. [21][22][23] The biologic data differ considerably between infants and older age groups and only slightly between children, adolescents, and young adults.…”

Section: Discussionmentioning

confidence: 99%

Significance of age in acute myeloid leukemia patients younger than 30 years

Creutzig

Büchner

Sauerland

et al. 2007

Cancer

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BACKGROUND. Data on the impact of age in acute myeloid leukemia (AML) patients <30 years treated in pediatric and adult trials are scarce. METHODS. In all, 891 patients <18 years were treated in the pediatric trials AML‐BFM 93/98 and 290 adolescents and young adults (>16 to <30 years) in the AMLCG 92/99 and AMLSG HD93/98A trials. Treatment schedules and dose intensities were comparable. RESULTS. Initial features and risk factors differed considerably between infants (<2 years) and older age groups and only slightly between children (2 to <13), adolescents (13 to <21) and young adults (21 to <30). Treatment results were most favorable in children (5‐year event free survival [EFS]: 54% ± 3%), slightly inferior in adolescents (46% ± 4%, P = .03), and unfavorable in young adults (28% ± 5%, P = .0001). Excluding patients with favorable karyotypes, the results were similar in infants and children (EFS: 44% ± 4% and 46% ± 3%, respectively) and inferior in adolescents (35% ± 4%) and young adults (23% ± 4%). There was an increased, age‐related percentage and inferior outcome in patients with >5% bone marrow blasts after induction. EFS was especially poor in young adults, with blasts >5%. The blast count after induction was of no prognostic value in patients with favorable karyotypes, but a significant risk factor in patients with other cytogenetics. CONCLUSIONS. Biologic data differed mainly between infants and older age groups. When comparing the same age groups, outcome was similar between the trial groups, which differed from reports concerning acute lymphoblastic leukemia. However, the prognosis decreased after childhood independent of other risk factors. This indicates that even in the younger cohorts increasing age may be an additional unfavorable factor. Cancer 2008. © 2007 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Significance of age in acute myeloid leukemia patients younger than 30 years

Creutzig

Büchner

Sauerland

et al. 2007

Cancer

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“…Although its significance as an in vivo resistance factor remains to be determined, expression of MRP2 has been reported for several types of human cancers that are relevant to the pump's resistance profile, including colorectal (camptothecins), breast and leukemia (anthracyclines), ovary (cisplatin) and others (for example, Hinoshita et al, 2000;Nies et al, 2001;Ohishi et al, 2002;Burger et al, 2003;Steinbach et al, 2003, and references therein). MRP2 plays a role in the hepatobiliary excretion of numerous pharmaceuticals (Suzuki and Sugiyama, 2002).…”

Section: Mrp2mentioning

confidence: 99%

The MRP family of drug efflux pumps

2003

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The MRP family is comprised of nine related ABC transporters that are able to transport structurally diverse lipophilic anions and function as drug efflux pumps. Investigations of this family have provided insights not only into cellular resistance mechanisms associated with natural product chemotherapeutic agents, antifolates and nucleotide analogs, but also into factors that influence drug distribution in the body, membrane systems that are involved in the extrusion of reduced folates, cysteinyl leukotrienes and bile acids, and the molecular basis of two hereditary conditions in humans. The review will describe the biochemical properties, drug resistance activities and potential in vivo functions of these unusual pumps.

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“…In pediatric patients it does not have a prognostic impact at all. 14,15 There could be two reasons for this age dependence. First, the expression of P-gp is higher in older individuals.…”

Section: Introductionmentioning

confidence: 99%

ABC transporters and drug resistance in leukemia: was P-gp nothing but the first head of the Hydra?

2007

Self Cite

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More than 30 years ago it was discovered that permeability glycoprotein (P-gp) can cause drug resistance. Over the following decades numerous studies showed that high expression of P-gp is associated with poor prognosis in acute myeloid leukemia in adults and that it causes multidrug resistance via ATP-dependent drug efflux. It was hoped that an inhibition of P-gp could sensitize resistant leukemic cells to chemotherapy and thus improve treatment results. Today we know that the family of ATP-binding cassette transporters (ABC transporters) comprises 48 different proteins. Some of them seem to be able to cause drug resistance as well as P-gp. This review focuses on emerging data on the clinical relevance of other ABC transporters, such as BCRP, MRP3, and ABCA3. When Heracles fought the ancient Hydra, he had to fight all the heads at ones but only one head was vital for the beast. Can we block all the relevant ABC transporters at once? Is there one transporter that is more important than the others?

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Contrary to adult patients, expression of the multidrug resistance gene (MDR1) fails to define a poor prognostic group in childhood AML

Cited by 29 publications

References 7 publications

Significance of age in acute myeloid leukemia patients younger than 30 years

Significance of age in acute myeloid leukemia patients younger than 30 years

The MRP family of drug efflux pumps

ABC transporters and drug resistance in leukemia: was P-gp nothing but the first head of the Hydra?

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