This study was directed to characterize the role of glutamine in the modulation of the response of chronic myeloid leukemia (CML) cells to low oxygen, a main condition of hematopoietic stem cell niches of bone marrow. Cells were incubated in atmosphere at 0.2% oxygen in the absence or the presence of glutamine. The absence of glutamine markedly delayed glucose consumption, which had previously been shown to drive the suppression of BCR/Abl oncoprotein (but not of the fusion oncogene BCR/abl) in low oxygen. Glutamine availability thus emerged as a key regulator of the balance between the pools of BCR/Abl protein-expressing and-negative CML cells endowed with stem/progenitor cell potential and capable to stand extremely low oxygen. These findings were confirmed by the effects of the inhibitors of glucose or glutamine metabolism. The BCR/Abl-negative cell phenotype is the best candidate to sustain the treatment-resistant minimal residual disease (MRD) of CML because these cells are devoid of the molecular target of the BCR/Abl-active tyrosine kinase inhibitors (TKi) used for CML therapy. Therefore, the treatments capable of interfering with glutamine action may result in the reduction in the BCR/Abl-negative cell subset sustaining MRD and in the concomitant rescue of the TKi sensitivity of CML stem cell potential. The data obtained with glutaminase inhibitors seem to confirm this perspective.

Glutamine availability controls bcr/abl protein expression and functional phenotype of chronic myeloid leukemia cells endowed with stem/progenitor cell potential / Poteti M.; Menegazzi G.; Peppicelli S.; Tusa I.; Cheloni G.; Silvano A.; Mancini C.; Biagioni A.; Tubita A.; Mazure N.M.; Lulli M.; Rovida E.; Dello Sbarba P. - In: CANCERS. - ISSN 2072-6694. - ELETTRONICO. - 13:(2021), pp. 4372-4378. [10.3390/cancers13174372]

Glutamine availability controls bcr/abl protein expression and functional phenotype of chronic myeloid leukemia cells endowed with stem/progenitor cell potential

Poteti M.;Menegazzi G.;Peppicelli S.;Tusa I.;Cheloni G.;Silvano A.;Mancini C.;Biagioni A.;Tubita A.;Lulli M.;Rovida E.
;
Dello Sbarba P
2021

Abstract

This study was directed to characterize the role of glutamine in the modulation of the response of chronic myeloid leukemia (CML) cells to low oxygen, a main condition of hematopoietic stem cell niches of bone marrow. Cells were incubated in atmosphere at 0.2% oxygen in the absence or the presence of glutamine. The absence of glutamine markedly delayed glucose consumption, which had previously been shown to drive the suppression of BCR/Abl oncoprotein (but not of the fusion oncogene BCR/abl) in low oxygen. Glutamine availability thus emerged as a key regulator of the balance between the pools of BCR/Abl protein-expressing and-negative CML cells endowed with stem/progenitor cell potential and capable to stand extremely low oxygen. These findings were confirmed by the effects of the inhibitors of glucose or glutamine metabolism. The BCR/Abl-negative cell phenotype is the best candidate to sustain the treatment-resistant minimal residual disease (MRD) of CML because these cells are devoid of the molecular target of the BCR/Abl-active tyrosine kinase inhibitors (TKi) used for CML therapy. Therefore, the treatments capable of interfering with glutamine action may result in the reduction in the BCR/Abl-negative cell subset sustaining MRD and in the concomitant rescue of the TKi sensitivity of CML stem cell potential. The data obtained with glutaminase inhibitors seem to confirm this perspective.
2021
13
4372
4378
Poteti M.; Menegazzi G.; Peppicelli S.; Tusa I.; Cheloni G.; Silvano A.; Mancini C.; Biagioni A.; Tubita A.; Mazure N.M.; Lulli M.; Rovida E.; Dello Sbarba P
File in questo prodotto:
File Dimensione Formato  
2021 Poteti et al Cancers.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 3.52 MB
Formato Adobe PDF
3.52 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1243148
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
social impact