Clinical Significance of ABCB1 in Acute Myeloid Leukemia: A Comprehensive Study

• Published in: Cancers Vol. 11; no. 9; p. 1323
• Main Authors: Boyer, Thomas, Gonzales, Fanny, Barthélémy, Adeline, Marceau-Renaut, Alice, Peyrouze, Pauline, Guihard, Soizic, Lepelley, Pascale, Plesa, Adriana, Nibourel, Olivier, Delattre, Carole, Wetterwald, Marc, Pottier, Nicolas, Plantier, Isabelle, Botton, Stéphane de, Dombret, Hervé, Berthon, Céline, Preudhomme, Claude, Roumier, Christophe, Cheok, Meyling
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.09.2019; MDPI
• Series: Cancers
• Subjects: ABCB1; Acute myeloid leukemia; Anthracycline; CD200 antigen; CD34 antigen; CD7 antigen; Chemotherapy; Clinical outcomes; Clinical significance; Cytogenetics; Drug resistance; Gemtuzumab ozogamicin; Gene expression; Genotype & phenotype; Leukemia; Life Sciences; Mutation; Myeloid leukemia; Patients; prognosis; Quinine; ABCB1; drug resistance; acute myeloid leukemia; prognosis; gene expression
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers11091323

ABCB1 is a member of the ATP binding cassette transporter family and high ABCB1 activity is considered as a poor prognostic factor in acute myeloid leukemia (AML) treated with intensive chemotherapy, its direct relation with drug resistance remains unclear. We evaluated ABCB1 activity in relation with clinical parameters and treatment response to standard chemotherapy in 321 patients with de novo AML. We assessed multiple clinical relationships of ABCB1 activity-ex vivo drug resistance, gene expression, and the ABCB1 inhibitor quinine were evaluated. ABCB1 activity was observed in 58% of AML and was linked to low white blood cell count, high expression of CD34, absence of , and absence of mutant . Moreover, ABCB1 activity was associated with worse overall- and event-free survival. However, ABCB1 activity did not directly lead to ex vivo drug resistance to anthracyclines. We found that was highly correlated with gene expressions of , and , indicating that expression maybe a passenger characteristic of high-risk AML. Furthermore, was inversely correlated to cluster genes and . Thus, low AML patients benefited specifically from anti-CD33 treatment by gemtuzumab ozogamicin in addition to standard chemotherapy. We showed prognostic importance of ABCB1 gene expression, protein expression, and activity. Furthermore, ABCB1 was not directly linked to drug resistance, ABCB1 inhibition did not improve outcome of high ABCB1 AML patients and thus high ABCB1 may represent a passenger characteristic of high-risk AML.