Correction: Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells

Abstract

The original version of this Article omitted the following from the Acknowledgements: This research was also supported by grants to KZ (UL and L-CNRS). This has now been corrected in both the PDF and HTML versions of the Article.

Gap Junctions in the Bone Marrow Lympho-Hematopoietic Stem Cell Niche, Leukemia Progression, and Chemoresistance

“…Interestingly, CBX induced disruption of functional GJ in the leukemic niche results in decreased oxidative phosphorylation in AML cells, revealing a major perturbation in mitochondrial function, and in increased chemosensitivity and apoptosis of leukemic cells. Its pro-apoptotic effect was synergized with chemotherapy drug cytarabine (AraC) [153]. These findings suggest a link between efficient tumor formation and recovery of mitochondrial respiration, and GJ participation in the protective effect offered by the leukemic niche via trafficking of whole functional mitochondria, facilitating leukemogenesis.…”

“…In a recent study, Kouzi et al delineate a higher expression of Cx25, Cx31.9, and Cx59 in AML blasts and BM CD34 + cells, while the differential expression of these connexins was independent of the cytogenetic or molecular status of AML cells. Of note, a higher level of transcription of Cx25, Cx26, Cx30, Cx31, Cx32, Cx36, Cx37, Cx40, Cx46, and Cx62 was observed in AML BMSC [153]. Likewise, a higher expression of Cx43 was detected in multiple myeloma (MM) cell lines (RPMI8226, U266, and XG7), primary cell as well as in BMSC.…”

“…Furthermore, higher expression of Cx25 and Cx40 in acute lymphoblastic leukemia (ALL) and AML cell lines, as well as in AML patient's cells play an important role in leukemia cell communication and chemoresistance. Inhibition of Cx25, however, decreases leukemic cell proliferation and sensitizes the cells to chemotherapy [153,161]. In a recent study, Kouzi et al delineate a higher expression of Cx25, Cx31.9, and Cx59 in AML blasts and BM CD34 + cells, while the differential expression of these connexins was independent of the cytogenetic or molecular status of AML cells.…”

“…Interestingly, a strong expansion of leukemic CD34 + cells and leukemic cobblestone-area formation was observed ex vivo after culture on BMSC [150][151][152], suggesting that in addition to communication via cytokines and extracellular matrix proteins, the expansion of leukemic cells is also influenced by cues provided through cell-to-cell contact with the BMME. Of note, disruption of GJ by carbenoxolone (CBX, a glycyrrhetinic acid derivative) in the co-culture of acute myelogenous leukemia (AML) cells with BMSC reduces the chemoresistance favored by the leukemic niche and enhances apoptosis [153]. Although CBX is not a GJ specific inhibitor, it has been proposed that by intercalating into the plasma membrane and binding to the GJ connexons, CBX induces a conformational change that results in closure of GJIC channels [136,154].…”

The mechanisms of mutual relationship between malignant hematologic cells and mesenchymal stem cells: Does it contradict the nursing role of mesenchymal stem cells?

“…Carbenoxolone-induced GJ disruption could interfere with MSC and different malignant hematologic cell line communication and alters drug resistance pattern [ 53 ]. It indicates the important role of GJ between these cells in the outcome of leukemia treatment.…”