BJH: Dexamethasone-mediated inhibition of Notch signaling blocks the interaction between leukemia and mesenchymal stromal cells

Acute myeloid leukemia (AML) is a hematological malignancy characterized by a poor prognosis

Acute myeloid leukemia (AML) is a hematological malignancy characterized by a poor prognosis

Therefore, a foreign research team tried to investigate this in order to improve the understanding of the signals related to the leukemia BM niche, and finally determine a novel and effective anti-leukemia treatment strategy

They used the previously described murine AML cell line, C1498 and MSCS isolated from control [wild type (WT) MSC] and leukemia mice (AML MSC)

Using the previously described murine AML cell line, C1498 and MSCS were isolated from the control [wild type (WT) MSC] and leukemia mice (AML MSC)

Murine and human acute myeloid leukemia (AML) Mesenchymal stromal cells (MSC) support the proliferation of leukemia cells Murine and human acute myeloid leukemia (AML) Mesenchymal stromal cells (MSC) support the proliferation of leukemia cells

They hypothesized that dexamethasone-mediated blockade of Notch signaling in AML MSCs may explain the therapeutic benefits observed in AML patients

They hypothesized that dexamethasone-mediated blockade of Notch signaling in AML MSCs may explain the therapeutic benefits observed in AML patients

Dexamethasone in vitro acute myeloid leukemia (AML) cells and the effect of the interaction between AML- mesenchymal stromal cells (MSC) dexamethasone in vitro mesenchymal stromal between acute myeloid leukemia (AML) cells and AML- The role of cell (MSC) interaction in vitro

In order to verify the results obtained using the murine AML cell line C1498 and primary murine MSC and prove that the results are not specific to the co-culture system, they used immortalized human MSC and the human AML cell line Kasumi-1, in order to verify the primary and immortal The phenotypes of MSCs are comparable, and their surface markers and their ability to differentiate into adipocytes, chondrocytes and bone cells were examined

To verify the results obtained using the murine AML cell line C1498 and primary murine MSC and prove that the results are not specific to the co-culture system, they used immortalized human MSC and the human AML cell line Kasumi-1, in order to verify the primary and immortal The phenotypes of MSCs are comparable, and their surface markers and their ability to differentiate into adipocytes, chondrocytes and bone cells were examined

Molecular characteristics of acute myeloid leukemia (AML) mesenchymal stromal cells (MSC) Molecular characteristics of acute myeloid leukemia (AML) mesenchymal stromal cells (MSC)

They evaluated the therapeutic effect of dexamethasone on the progression and survival of leukemia in MLL-AF9 transgenic leukemia mice, and whether dexamethasone also affected Notch signaling in the body

They evaluated the therapeutic effect of dexamethasone on the progression and survival of leukemia in MLL-AF9 transgenic leukemia mice, and whether dexamethasone also affected Notch signaling in the body

The effect of dexamethasone on the interaction between acute myeloid leukemia (AML) cells and AML-mesenchymal stromal cells (MSC) in vivo ) The role of in vivo interactions

Their data, especially in AML MSC, demonstrated the enrichment of the Notch marker gene set and the activation of Notch signaling

Their data, especially in AML MSC, demonstrated the enrichment of the Notch marker gene set and the activation of Notch signaling

Dexamethasone treatment of interfering leukemia and acute myeloid leukemia (AML)-mesenchymal stromal cell (MSC) interaction Dexamethasone treatment of interfering leukemia and acute myeloid leukemia (AML)-mesenchymal stromal cells (MSC) interaction

Studies have demonstrated the functional difference between leukemia-derived MSC (AML MSC) and healthy donors (HD MSC)

Studies have demonstrated the functional difference between leukemia-derived MSC (AML MSC) and healthy donors (HD MSC)

At the same time, Notch inhibitors only have a slight effect on leukemia cells, but they strongly affect Notch signaling in AML MSCs and cancel their cytoprotective function on AML cells

In conclusion, the use of dexamethasone or Notch inhibitors to target the interaction of leukemia cells and AML MSCs may further improve the treatment outcome of AML patients
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Using dexamethasone or Notch inhibitors to target the interaction of leukemia cells and AML MSCs may further improve treatment outcomes for AML patients

 

Original source:

Original source:

Ahmed, HMM, Nimmagadda, SC, Al-Matary, YS, Fiori, M.
, May, T.
, Frank, D.
, Patnana, PK, Récher, C.
, Schliemann, C.
, Mikesch, J.
-H.
, Koenig, T.
, Rosenbauer, F.
, Hartmann, W.
, Tuckermann, J.
, Dührsen, U.
, Lanying, W.
, Dugas, M.
, Opalka, B.
, Lenz, G.
and Khandanpour, C.
(2021), Dexamethasone-mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells.
Br J Haematol.
  https://doi.
org/10.
1111/bjh.
17940

Ahmed, HMM, Nimmagadda, SC, Al-Matary, YS, Fiori, M.
, May, T.
, Frank, D.
, Patnana, PK, Récher, C.
, Schliemann, C.
, Mikesch, J.
-H.
, Koenig, T.
, Rosenbauer, F.
, Hartmann, W.
, Tuckermann, J.
, Dührsen, U.
, Lanying, W.
, Dugas, M.
, Opalka, B.
, Lenz, G.
and Khandanpour, C.
(2021), Dexamethasone-mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells.
Br J Haematol.
  https://doi.
org/10.
1111/bjh.
17940 https://doi.
org/10.
1111/bjh.
17940

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