Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting

Chiarini, Francesca; Lonetti, Annalisa; Evangelisti, Camilla; Buontempo, Francesca; Orsini, Ester; Evangelisti, Cecilia; Cappellini, Alessandra; Neri, Luca M.; McCubrey, James A.; Martelli, Alberto M.

doi:10.1016/j.bbamcr.2015.08.015

Cited by 120 publications

(124 citation statements)

References 192 publications

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“…Activated WNT by BM microenvironment protects B-ALL from death to chemotherapy [20]. Furthermore, B-ALL cells express increase phosphorylation which inhibit glycogen synthase 3 (GSK3) β which acts as β-catenin inhibitor [8]. Treatment with β -catenin inhibitor (XAV939) sensitized leukemia cells to therapy [21].…”

Section: Wnt/β-catenin Signalingmentioning

confidence: 99%

“…Up-regulates WNT signaling pathway under hypoxic condition in T-ALL, leading to WNT/β-catenin and HIF1 α support T-ALL cells [24]. Different strategy is developing targeting HIF1 α to exert hypoxia pro-survival effects of neoplastic cells [8].…”

Section: Hypoxiamentioning

confidence: 99%

“…The hypoxic tumor is found to be more resistance to chemotherapy. The most known marker of hypoxia is Hypoxia inducible factor 1α (HIF1α) [8].…”

Section: Hypoxiamentioning

confidence: 99%

“…When leukemic cells grow, they disrupt normal hematopoietic progenitor cell (HPC) bone marrow niches and create abnormal microenvironments. Also, niches have been linked to the development of drug resistance [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…ALL can also affect those between 15 and 25 years old, as well as elderly people. In 2010, 8.257 people in the UK were diagnosed with leukaemia [4]. Leukaemia is more common in males than in females [3].…”

Section: Introductionmentioning

confidence: 99%

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Microenvironment and its role in acquire drug resistance of leukemia treatment

Qattan¹

2016

J Stem Cell Res Med

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Bone marrow niche is the microenvironment where the leukemic cells residue and it support cell proliferation, metastasis, and drug resistance by secretion of numerous factors including cytokines. When leukemic cells grow, they disrupt normal hematopoietic progenitor cell (HPC) bone marrow niches and create abnormal microenvironments. Also, niches recently have been linked to the development of drug resistance. One type of stem cell that resides in the bone marrow niche is called Mesenchymal stem cells (MSCs). Two microenvironment niches have been identified in BM; Osteoblastic and vascular, these niches provide the area in where the leukemia cells can escape from the chemotherapy-induced death and acquire drug resistance cells. Moreover, this review highlight briefly the role of exosomes in cell-to-cell communication and progression. The interaction between BM and leukemia cells through different proteins including cytokines, adhesion molecule, signal transduction pathways and hypoxia are mentioned simply.MSCs have potential successful uses in regenerative medicine, but in this short review focusing on their potential role in supporting resistance in leukemia and the progress in elucidating the cellular components of HSC in BM.

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Section: Wnt/β-catenin Signalingmentioning

confidence: 99%

Section: Hypoxiamentioning

confidence: 99%

“…The hypoxic tumor is found to be more resistance to chemotherapy. The most known marker of hypoxia is Hypoxia inducible factor 1α (HIF1α) [8].…”

Section: Hypoxiamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microenvironment and its role in acquire drug resistance of leukemia treatment

Qattan¹

2016

J Stem Cell Res Med

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Enforced sialyl‐Lewis‐X (sLeX) display in E‐selectin ligands by exofucosylation is dispensable for CD19‐CAR T‐cell activity and bone marrow homing

Sánchez-Martínez

Gutiérrez-Agüera

Romecín

et al. 2021

Clinical & Translational Med

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CD19‐directed chimeric antigen receptors (CAR) T cells induce impressive rates of complete response in advanced B‐cell malignancies, specially in B‐cell acute lymphoblastic leukemia (B‐ALL). However, CAR T‐cell‐treated patients eventually progress due to poor CAR T‐cell persistence and/or disease relapse. The bone marrow (BM) is the primary location for acute leukemia. The rapid/efficient colonization of the BM by systemically infused CD19‐CAR T cells might enhance CAR T‐cell activity and persistence, thus, offering clinical benefits. Circulating cells traffic to BM upon binding of tetrasaccharide sialyl‐Lewis X (sLeX)‐decorated E‐selectin ligands (sialofucosylated) to the E‐selectin receptor expressed in the vascular endothelium. sLeX‐installation in E‐selectin ligands is achieved through an ex vivo fucosylation reaction. Here, we sought to characterize the basal and cell‐autonomous display of sLeX in CAR T‐cells activated using different cytokines, and to assess whether exofucosylation of E‐selectin ligands improves CD19‐CAR T‐cell activity and BM homing. We report that cell‐autonomous sialofucosylation (sLeX display) steadily increases in culture‐ and in vivo‐expanded CAR T cells, and that, the cytokines used during T‐cell activation influence both the degree of such endogenous sialofucosylation and the CD19‐CAR T‐cell efficacy and persistence in vivo. However, glycoengineered enforced sialofucosylation of E‐selectin ligands was dispensable for CD19‐CAR T‐cell activity and BM homing in multiple xenograft models regardless the cytokines employed for T‐cell expansion, thus, representing a dispensable strategy for CD19‐CAR T‐cell therapy.

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Post‐hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors

Roshandel

Tavakoli

Parkhideh

et al. 2022

Health Science Reports

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Background and Aims Despite the revolutionary effects of hematopoietic stem cell transplantation (HSCT) in treating hematological malignancies, post‐HSCT relapse is considered a critical concern of clinicians. Residual malignant cells employ many mechanisms to evade immune surveillance and survive to cause relapse after transplantation. One of the immune‐frustrating mechanisms through which malignant cells can compromise the antitumor effects is misusing the self‐limiting system of immune response by overexpressing inhibitory molecules to interact with the immune cells, leading them to so‐called “exhausted” and ineffective. Introduction of these molecules, known as immune checkpoints, and blocking them was a prodigious step to decrease the relapses. Methods Using keywords nivolumab , pembrolizumab , and ipilimumab , we investigated the literature to figure out the role of the immune checkpoints in the HSCT setting. Studies in which these agents were administrated for relapse after transplantation were reviewed. Factors such as the interval from the transplant to relapse, previous treatment history, adverse events, and the patients’ outcome were extracted. Results Here we provided a mini‐review discussing the experiences of three immune checkpoints, including nivolumab, pembrolizumab, and ipilimumab, as well as the pros and cons of using their blockers in relapse control after HSCT. In conclusion, it seems that CI therapy seems effective for this population. Future investigations may provide detailed outlook of this curative options.

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Advances in understanding the acute lymphoblastic leukemia bone marrow microenvironment: From biology to therapeutic targeting

Cited by 120 publications

References 192 publications

Microenvironment and its role in acquire drug resistance of leukemia treatment

Microenvironment and its role in acquire drug resistance of leukemia treatment

Enforced sialyl‐Lewis‐X (sLeX) display in E‐selectin ligands by exofucosylation is dispensable for CD19‐CAR T‐cell activity and bone marrow homing

Post‐hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors

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