Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway
P-glycoprotein (known as ABCB1 transporter) expression in myeloid blasts of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) leads to the commonly observed multidrug resistance. Overexpression of latrophilin-1 was detected in leukemic cells from AML patients. In a previous study, we sh...
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/2072-6694/13/14/3629 |
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| author | Zuzana Kocibalova Martina Guzyova Ivana Borovska Lucia Messingerova Lucia Copakova Zdena Sulova Albert Breier |
| author_facet | Zuzana Kocibalova Martina Guzyova Ivana Borovska Lucia Messingerova Lucia Copakova Zdena Sulova Albert Breier |
| author_sort | Zuzana Kocibalova |
| collection | DOAJ |
| description | P-glycoprotein (known as ABCB1 transporter) expression in myeloid blasts of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) leads to the commonly observed multidrug resistance. Overexpression of latrophilin-1 was detected in leukemic cells from AML patients. In a previous study, we showed that ABCB1 overexpression is associated with decreased latrophilin-1 expression in MOLM-13/VCR and SKM-1/VCR AML cell variants derived from MOLM-13 and SKM-1 cells by vincristine selection/adaptation. In the present study, we found that if ABCB1 overexpression occurs in myeloid blasts of newly diagnosed MDS patients, latrophilin-1 expression is attenuated. Latrophilin-1 may initiate TIM-3- and galectin-9-mediated immune escape. We demonstrated changes in the expression of both proteins by comparing ABCB1-positive cell variants (MOLM-13/VCR, SKM-1/VCR) with their ABCB1-negative counterparts. Galectin-9 was present in our cell lines in eight protein isoforms for which we identified the respective transcription variants resulting from alternative splicing, and we verified their structure by sequencing. The isoform profile of galectin-9 was different between ABCB1-positive and ABCB1-negative cell variants. The interaction partner of galectin-9 is CD44, and its expression was altered in the ABCB1-positive variants MOLM-13/VCR and SKM-1/VCR compared to their ABCB1-negative counterparts. |
| first_indexed | 2024-03-10T09:43:14Z |
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| id | doaj.art-8303f006d9b54e0da612d33a8f35ac1b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T09:43:14Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-8303f006d9b54e0da612d33a8f35ac1b2023-11-22T03:26:34ZengMDPI AGCancers2072-66942021-07-011314362910.3390/cancers13143629Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling PathwayZuzana Kocibalova0Martina Guzyova1Ivana Borovska2Lucia Messingerova3Lucia Copakova4Zdena Sulova5Albert Breier6Faculty of Chemical and Food Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, SlovakiaFaculty of Chemical and Food Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, SlovakiaDepartment of Biochemistry and Cytochemistry, Institute of Molecular Physiology and Genetics, Centre of Bioscences SAS, Slovak Academy of Sciences, Dúbravská cesta 9, 840 05 Bratislava, SlovakiaFaculty of Chemical and Food Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, SlovakiaNational Cancer Institute, Klenová 1, 833 10 Bratislava, SlovakiaDepartment of Biochemistry and Cytochemistry, Institute of Molecular Physiology and Genetics, Centre of Bioscences SAS, Slovak Academy of Sciences, Dúbravská cesta 9, 840 05 Bratislava, SlovakiaFaculty of Chemical and Food Technology, Institute of Biochemistry and Microbiology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, SlovakiaP-glycoprotein (known as ABCB1 transporter) expression in myeloid blasts of acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) leads to the commonly observed multidrug resistance. Overexpression of latrophilin-1 was detected in leukemic cells from AML patients. In a previous study, we showed that ABCB1 overexpression is associated with decreased latrophilin-1 expression in MOLM-13/VCR and SKM-1/VCR AML cell variants derived from MOLM-13 and SKM-1 cells by vincristine selection/adaptation. In the present study, we found that if ABCB1 overexpression occurs in myeloid blasts of newly diagnosed MDS patients, latrophilin-1 expression is attenuated. Latrophilin-1 may initiate TIM-3- and galectin-9-mediated immune escape. We demonstrated changes in the expression of both proteins by comparing ABCB1-positive cell variants (MOLM-13/VCR, SKM-1/VCR) with their ABCB1-negative counterparts. Galectin-9 was present in our cell lines in eight protein isoforms for which we identified the respective transcription variants resulting from alternative splicing, and we verified their structure by sequencing. The isoform profile of galectin-9 was different between ABCB1-positive and ABCB1-negative cell variants. The interaction partner of galectin-9 is CD44, and its expression was altered in the ABCB1-positive variants MOLM-13/VCR and SKM-1/VCR compared to their ABCB1-negative counterparts.https://www.mdpi.com/2072-6694/13/14/3629latrophilin-1TIM-3galectin-9ABCB1CD44acute myeloid leukemia |
| spellingShingle | Zuzana Kocibalova Martina Guzyova Ivana Borovska Lucia Messingerova Lucia Copakova Zdena Sulova Albert Breier Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway Cancers latrophilin-1 TIM-3 galectin-9 ABCB1 CD44 acute myeloid leukemia |
| title | Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway |
| title_full | Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway |
| title_fullStr | Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway |
| title_full_unstemmed | Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway |
| title_short | Development of Multidrug Resistance in Acute Myeloid Leukemia Is Associated with Alterations of the LPHN1/GAL-9/TIM-3 Signaling Pathway |
| title_sort | development of multidrug resistance in acute myeloid leukemia is associated with alterations of the lphn1 gal 9 tim 3 signaling pathway |
| topic | latrophilin-1 TIM-3 galectin-9 ABCB1 CD44 acute myeloid leukemia |
| url | https://www.mdpi.com/2072-6694/13/14/3629 |
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