In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia

Espinoza-Hernández, Laura Eugenia; Cruz-Rico, Jorge; Benítez‐Aranda, Herminia; Martı́nez-Jaramillo, Guadalupe; Rodrı́guez-Zepeda, Maria del Carmen; Vélez-Ruelas, Maria Antonieta; Mayani, Héctor

doi:10.1016/s0145-2126(00)00141-7

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…The in vitro TLR ligation on CD34+ cells from ALL pediatric patients induce cell proliferation and redirection of cell fates (Dorantes-Acosta et al, unpublished data). Along with recurrent infections, increasing evidence suggests the prevalence of inflammatory environments in hematological abnormalities such as acute leukemias [56, 91], remaining to be addressed if overproduction of inflammatory cytokines impacts the HSC niches and can stimulate aberrant cell fate decisions.…”

Section: Potential Mechanisms Of Lineage Conversionmentioning

confidence: 99%

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

Dorantes-Acosta

Pelayo

2012

Bone Marrow Research

117

115

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Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

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Section: Potential Mechanisms Of Lineage Conversionmentioning

confidence: 99%

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

Dorantes-Acosta

Pelayo

2012

Bone Marrow Research

117

115

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“…In hematological abnormalities such as acute leukemias, increasing evidence suggests the prevalence of inflammatory environments, along with recurrent infections and chemotherapy-associated damage, strengthening the possibility that TLR-expressing primitive cells represent the beginning of instability of the lineage [21, 22]. Whether these signals contribute to disease or promote lineage conversion in relapsed leukemia are currently topical questions.…”

Section: Introductionmentioning

confidence: 99%

TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

Dorantes-Acosta

Vadillo

Contreras-Quiroz

et al. 2013

BioMed Research International

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Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs) in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

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“…This cytokine is a strong activator of the JAK/ STAT pathway and induces cell proliferation and inhibits apoptosis via cyclins, c-myc and bcl-2. Notably, in bone marrow of ALL patients IL-6 is increased and its levels correlate with the severity of disease [41].…”

Section: Leukemic Niche: Guilty Of Aiding and Abettingmentioning

confidence: 99%

A Sanctuary for cancer cells: Microenvironment in T-cell acute lymphoblastic leukemia survival and drug resistance

Giacomo¹,

Fiore²,

Kyriakides³

et al. 2017

Clin Diagn Pathol

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T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy associated with a high risk of treatment failure. Efforts to improve outcomes have focused on underlying genetic defects. However, strong evidence suggests that leukemic cells prime a maladapted niche that in turn provides signals capable of sustaining the dormancy of leukemia initiating cells and protects them from toxic chemotherapeutic agents. Here, we aim to describe how key components of the bone marrow microenvironment are essential for leukemia initiation and progression. Although many mechanisms have been recently discovered, further studies are required to fully dissect the molecular mechanisms governing the bidirectional interactions between tumor and host cells. We predict that these new discoveries will pave the way for the implementation of novel therapeutic strategies and will eventually lead to the eradication of the drug-resistant cells, substantially and ultimately enhancing cure rates for T-ALL patients.

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In vitro characterization of the hematopoietic system in pediatric patients with acute lymphoblastic leukemia

Cited by 19 publications

References 22 publications

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

A Sanctuary for cancer cells: Microenvironment in T-cell acute lymphoblastic leukemia survival and drug resistance

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