Expression of the Human ATP-Binding Cassette Transporter Superfamily in Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1179-1179
Author(s):  
Maria Ho ◽  
Donna E. Hogge ◽  
Victor Ling
Keyword(s):  
Acute Myeloid Leukemia ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Normal Blood ◽  
Atp Binding ◽  
Normal Peripheral Blood ◽  
Acute Myeloid ◽  
Atp Binding Cassette

Abstract Members of the ATP-Binding-Cassette (ABC) transporter superfamily of proteins are involved in resistance to multiple chemotherapeutic drugs ( Multidrug Resistance or MDR) in a variety of malignant cells including leukemic blasts. Overexpression of some ABC transporters has been demonstrated in acute myeloid leukemia (AML) and is associated with clinical MDR and failure of conventional chemotherapy, which occurs frequently in this leukemia. Recent studies have also demonstrated ABC transporter expression in primitive normal hematopoietic cells, including progenitors which may give rise to AML after malignant transformation. In this study we used quantitative Real-Time PCR to assess and compare the expression level of all 47 known human ABC transporters in AML blasts and normal peripheral blood. Peripheral blood blasts from 17 patients with newly-diagnosed AML who subsequently received conventional remission induction therapy with cytosine arabinoside and daunorubicin were studied; 11 of these subsequently achieved complete remission of their leukemia while the remaining 6 had chemotherapy refractory disease. Contrary to expectations, no consistent difference in mRNA levels was found between the chemotherapy responsive and refractory groups of patient samples for any ABC transporter, including known MDR-related members such as MDR-1 and BCRP. Profiling of the 47 ABC transporters in 12 normal peripheral blood samples (6 mobilized with G-CSF, 6 non-mobilized) showed that TAP1 and MRP3 were 3.3-fold (P = 0.032) and 24-fold (P = 0.012), respectively, higher in normal donors as compared to AML patients. ABCA7, ABCB8, MRP3, MRP7, ALDP, PMP70 and PMP69 were greater than 3-fold higher (P < 0.05) in G-CSF-mobilized as compared to steady state normal blood. These results suggest that levels of ABC transporter mRNA expression in AML blasts prior to chemotherapy are not predictive of treatment response. This raises questions regarding the role of ABC transporters in intrinsic as opposed to induced or acquired chemotherapy drug resistance, which in turn has important implications in clinical usage of ABC-reversal agents. In addition, we identified expression of a variety of ABC transporters in both AML blasts and normal blood cells suggesting that this class of transporter proteins may have importance in both normal and malignant hematopoiesis.

scholarly journals Expression of some ATP-binding cassette transporters in acute myeloid leukemia

2017 ◽  
Vol 9 (4) ◽  
Author(s):  
Antonella Maria Salvia ◽  
Flavia Cuviello ◽  
Sabrina Coluzzi ◽  
Roberta Nuccorini ◽  
Immacolata Attolico ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Abc Transporters ◽  
Healthy Subjects ◽  
Myeloid Leukemia ◽  
Resistance Mechanisms ◽  
Atp Binding ◽  
Atp Binding Cassette Transporters ◽  
Acute Myeloid ◽  
Atp Binding Cassette

Hematopoietic cells express ATP binding cassette (ABC) transporters in relation to different degrees of differentiation. One of the known multidrug resistance mechanisms in acute myeloid leukemia (AML) is the overexpression of efflux pumps belonging to the superfamily of ABC transporters such as ABCB1, ABCG2 and ABCC1. Although several studies were carried out to correlate ABC transporters expression with drug resistance, little is known about their role as markers of diagnosis and progression of the disease. For this purpose we investigated the expression, by real-time PCR, of some ABC genes in bone marrow samples of AML patients at diagnosis and after induction therapy. At diagnosis, ABCG2 was always down-regulated, while an up regulated trend for ABCC1 was observed. After therapy the examined genes showed a different expression trend and approached the values of healthy subjects suggesting that this event could be considered as a marker of AML regression. The expression levels of some ABC transporters such as ABCC6, seems to be related to gender, age and to the presence of FLT3/ITD gene mutation.

ATP-binding cassette (ABC) proteins in untreated acute myeloid leukemia (AML) in patients 60 years and older (CALGB 9760)

2005 ◽  
Vol 23 (16_suppl) ◽  
pp. 6551-6551
Author(s):  
M. R. Baer ◽  
J. S. Shoemaker ◽  
R. Barrier ◽  
N. W. Cuviello ◽  
K. L. O’Loughlin ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Atp Binding ◽  
Abc Proteins ◽  
Acute Myeloid ◽  
Atp Binding Cassette

Expression of three different ATP-binding cassette transporters and correlation to chemoresistance in acute myeloid leukemia

2014 ◽  
Vol 37 (1) ◽  
pp. e7-e10 ◽  
Author(s):  
D. Palaiologou ◽  
P. Panayiotidis ◽  
G. Papanikolaou ◽  
G. Georgiou ◽  
G. Boutsikas ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Atp Binding ◽  
Atp Binding Cassette Transporters ◽  
Acute Myeloid ◽  
Atp Binding Cassette

High Expression of MDR1 and BCRP1 in Leukemic Stem Cells Correlates with Reversible Drug Resistance Ex Vivo and Predicts Failure of Remission Induction Chemotherapy in Patients with Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3385-3385
Author(s):  
Maria M. Ho ◽  
Donna E. Hogge ◽  
Victor Ling
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Myeloid Leukemia ◽  
Drug Sensitivity ◽  
Ex Vivo ◽  
Leukemic Stem Cells ◽  
Acute Myeloid

Abstract Although overexpression of members of the ATP-Binding-Cassette (ABC) transporter superfamily has been implicated in chemotherapy failure in acute myeloid leukemia (AML) in some studies, results have been conflicting. Previously we found no consistent difference in pre-treatment ABC transporter expression when comparing total blasts of 18 patients achieving complete remission (CR) and 13 patients who were refractory to induction chemotherapy (NR). However, among the CD34+CD38− AML cells (enriched for candidate “leukemic stem cells” which engraft in immunodeficient mice), as assessed by quantitative RT-PCR, elevated expression of MDR1 and/or BCRP1, two ABC transporters associated with drug resistance, was found in 8/10 NR patients as compared to 0/7 CR patients. No difference between CR and NR samples was observed in the more differentiated CD34+CD38+ or CD34− AML cells while none of the subpopulations showed a significant difference in MRP1 expression between CR and NR patient samples. To determine if this difference in gene expression was associated with altered functional activity of MDR1/BCRP1, the relative sensitivity of subpopulations of AML cells to induction of apoptosis following ex vivo treatment with daunorubicin with or without ABC inhibitors (PSC-833 and Verapamil) was assessed. All subpopulations of AML cells isolated from 2 CR patients showed similar drug sensitivity profiles (IC50 <0.04 μg/ml). In contrast, CD34+CD38− cells from 6 NR patients were more resistant to daunorubicin-induced apoptosis (p<0.05 for comparison of IC50s between CR and NR samples). ABC transporter inhibition in CD34+CD38− cells did not change daunorubicin sensitivity in CR samples, but increased drug sensitivity in a dose-dependent manner in NR samples, particularly in the CD34+CD38− fraction. This suggests a role for ABC transporters in sustaining a population of chemotherapy resistant leukemic stem cells which may allow survival of the malignant clone in patients following induction therapy. If the value of measuring MDR1/BCRP1 expression among these cells in predicting chemotherapy outcome is confirmed in a larger patient population, it may be possible to use such analysis to modify therapy for individual AML patients to overcome drug resistance.

Rapid rate of peripheral blood blast clearance accurately predicts complete remission in acute myeloid leukemia

Leukemia ◽  
2013 ◽  
Vol 28 (3) ◽  
pp. 713-716 ◽  
Author(s):  
V Vainstein ◽  
S A Buckley ◽  
O Shukron ◽  
E H Estey ◽  
J L Abkowitz ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Rapid Rate ◽  
Acute Myeloid

A CLINICOPATHOLOGICAL STUDY OF ACUTE AND CHRONIC LEUKEMIA IN A TERTIARY CARE HOSPITAL

2021 ◽  
pp. 72-74
Author(s):  
Sarat Das ◽  
Prasanta Kr. Baruah ◽  
Sandeep Khakhlari ◽  
Gautam Boro
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Blood ◽  
Myeloid Leukemia ◽  
Blood Smear ◽  
Lymphoblastic Leukemia ◽  
Peripheral Blood Smear ◽  
Care Hospital ◽  
Cytochemical Study ◽  
Acute Myeloid

Introduction: Leukemias are neoplastic proliferations of haematopoietic stem cells and form a major proportion of haematopoietic neoplasms that are diagnosed worldwide. Typing of leukemia is essential for effective therapy because prognosis and survival rate are different for each type and sub-type Aims: this study was carried out to determine the frequency of acute and chronic leukemias and to evaluate their clinicopathological features. Methods: It was a hospital based cross sectional study of 60 patients carried out in the department of Pathology, JMCH, Assam over a period of one year between February 2018 and January 2019. Diagnosis was based on peripheral blood count, peripheral blood smear and bone marrow examination (as on when available marrow sample) for morphology along with cytochemical study whenever possible. Results: In the present study, commonest leukemia was Acute myeloid leukemia (AML, 50%) followed by Acute lymphoblastic leukemia (ALL 26.6%), chronic myeloid leukemia (CML, 16.7%) and chronic lymphocytic leukemia (CLL, 6.7%). Out of total 60 cases, 36 were male and 24 were female with Male:Female ratio of 1.5:1. Acute lymphoblastic leukemia was the most common type of leukemia in the children and adolescents. Acute Myeloid leukemia was more prevalent in adults. Peripheral blood smear and bone Conclusion: marrow aspiration study still remains the important tool along with cytochemistry, immunophenotyping and cytogenetic study in the diagnosis and management of leukemia.

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