The further investigation was performed by using MEM M antib

The further investigation was performed by using MEM-M6/6 antibody to observe the linkage exits between CD147 and P-gp activity by intracellular Rho123 accumulation. MEM-M6/6 treatment did not alter Rho123 accumulation in drug-resistant K562/ADR cells. In contrast, the fluorescence intensity of Rho123 was significantly high in K562/ADR those times treated with curcumin, which is a P-gp modulator used as a positive control [27]. These results indicated that the decreased expression of CD147 by anti-CD147 MEM-M6/6 did not affect the P-gp function. It has been suggested that CD147 is involved in leukemia drug resistance by down-regulating Pgp, but not related to its drug efflux function [28,29]. Triggering of CD147 by MEM-M6/6 anti-CD147 mAb decreased expression of CD147 and caused downregulation of P-gp, but had no effect on P-gp function. Most strategies to reverse MDR phenotype in cancer cells have used drug efflux modulators. Moreover, to avoid MDR could be downregulated the expression of the target gene that involved in MDR such as MDR1 gene. Therefore, we propose regulating CD147 expression as a new strategy to overcome MDR. In summary, the CD147 involved the MDR phenotype of leukemic cells by regulating P-gp expression.
Acknowledgments This work was supported by the Thailand Research Fund (TRF) (RSA5580030), Chiang Mai University Research Fund (H-M5704), the TRF Senior Research Scholar (RTA5980007), the National Research University Project under Thailand\'s Office of the Higher Education Commission and supported in part by the grant from Center of Excellence on Medical Biotechnology (CEMB)/PERDO. Biomedical Technology Research Center is a Center of Excellence of Chiang Mai University.
Introduction Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by clonal expansion of blasts (myeloid progenitors) in the bone marrow and peripheral blood. Formerly, AML had a very poor prognosis; due to improvement in therapeutic regimens and supportive care (e.g. anti-infective drugs, blood transfusion support), AML is now cured in approximately 35–40% of patients younger with age younger than 60 years [1]. For elderly patients (>60 years), the prognosis has also improved, but overall remains adverse. Molecular screening plays a major role in prognostic categorization and subsequent definition of treatment strategies in AML. Cytogenetic abnormalities (e.g. deletions, translocations), as detectable in approximately 50% of adult patients with primary AML have long been associated with and recognized cause [2]. Of these, for example alterations of chromosomes 5, 7, 11q23 and a complex karyotype (described as >3 chromosomal abnormalities) were shown to associate with poor response to therapy and shorter overall survival (OS) while the presence of other cytogenetic abnormalities like t(15;17)(q22;q12), t(8;21)(q22;q22) or inv(16)(p13.1;q22) indicate longer disease remission and patient survival [1,3]. In contrast, about 40–50% of all AML cases are cytogenetically normal AML (CN-AML) [3]. CN-AMLs are considered to have an intermediate risk for relapse. However, with respect to clinical outcome substantial heterogeneity is observed in this group, which indicates that further prognostic markers to be evaluated. More recently, the identification of mutations by gene sequencing has provided novel prognostic and potentially therapeutical tools for patients with AML.
Prognosis/risk stratification Besides age and performance status, cytogenetic and molecular aberrations are the most important tools to predict outcome in AML [3]. In 2010, the European LeukemiaNet (ELN) classification scheme was created with the aim to standardize risk stratification in adult AML patients by including cytogenetic and known molecular abnormalities [4]. Patients are classified into one of four risk groups: favorable, intermediate 1, intermediate 2 and adverse (Table 1). Of note, acute promyelocytic leukemia (APL) is excluded from the ELN classification and also not discussed in this review, as APL requires highly specific prognostic, therapy and monitoring approaches that are largely different from those applied to other forms of AML.