Targeting Leukemia Stem Cells: Which Pathways Drive Self-Renewal Activity in T-Cell Acute Lymphoblastic Leukemia?

Belmonte, Miriam; Hoofd, Catherine; Weng, Andrew P.; Giambra, Vincenzo

doi:10.3747/co.23.2806

Cited by 20 publications

(20 citation statements)

References 79 publications

(107 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We could identify 94 gene products and 47 molecular pathways that had close to 1 AUC scores for the ALL-normal comparison (Supplementary dataset S4, Table 1). Among those, branches of Akt signaling [24], cAMP [25], cytoplasmic and mitochondrial apoptosis [26], PTEN [27], ATM checkpoint [28], Hedgehog [29], HGF [30], GSK3 [31], Estrogen and Glucocorticoid reception [32, 33], IGF1R [34], IL2 [35], TNF [36], ILK [37], JAK-STAT [38], JNK [39], mTOR [40], TGF-beta [41], Ras [42], PPAR [43], NGF [44], VEGF [45], Wnt [46], HIF1 and Notch signaling [47] were previously reported in the literature as ALL-associated pathways. However, the identified GPCR and TRAF-associated apoptosis marker pathways were new, thus representing ~4% of the total ALL-specific pathways.…”

Section: Resultsmentioning

confidence: 99%

Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells

Petrov

Suntsova

Mutorova

et al. 2016

Aging

View full text Add to dashboard Cite

Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells

Petrov

Suntsova

Mutorova

et al. 2016

Aging

View full text Add to dashboard Cite

show abstract

“…57 This data derives from solid tumor investigation; evidence is still needed in relation to leukemia, but those trials definitely demonstrated the complex and ambiguous role of HIFs in cancer.…”

Section: Perspectives and Conclusionmentioning

confidence: 99%

TThe role of hypoxia-inducible factors in leukemias

Szymczak¹,

Dybko²,

Kuliczkowski³

2018

Adv Clin Exp Med

View full text Add to dashboard Cite

Hypoxia, understood as low partial oxygen pressure, has become one of the most explored fields in recent years. Cellular response to hypoxia is mediated by hypoxia-inducible factors (HIFs) -potent transcription regulators, and their downstream pathways. In general, HIFs modify energy metabolism, inflammation and immune response, enhance cancer invasion, metastasis, resistance to treatment, and relapse. The influence of HIFs on the progression of leukemia is still under investigation in various studies, but in mice and some human models HIFs have been recognized as leukemia immortalizers by promoting leukemic stem cell quiescence and inhibiting their cell cycle. This makes leukemic stem cells resistant to most known treatment approaches. The role of HIFs in solid tumors and leukemia makes them almost ideal targets for an anticancer treatment. Although the first attempts with new molecules are encouraging, there is a need to investigate the ambiguous role of HIFs to develop a modern antileukemic treatment.

show abstract

“…RNA purity was verified by OD 260 /OD 280 nm absorption ratio. Complementary DNA (cDNA) was synthesized using SuperScript ™ First Strand Synthesis System for reverse transcriptase-polymerase chain reaction (RT-PCR; Invitrogen, USA), 2 µg of total RNA, and Oligo(dT) [12][13][14][15][16][17][18] Primers according to the manufacturer's instructions.…”

Section: Total Rna Extraction and Complementary Dna Synthesismentioning

confidence: 99%

“…9 Deregulated activation of the canonical Wnt pathway is also observed in leukemia. 1,[10][11][12][13] The hematopoietic system of the adult organism is composed of cells with a short life span, which are renewed by differentiating from a small population of hematopoietic stem cells (HSCs). Nuclear β-catenin is a key molecule that drives self-renewal.…”

Section: Introductionmentioning

confidence: 99%

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

et al. 2017

View full text Add to dashboard Cite

Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/β-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/β-catenin pathway antagonists-secreted frizzledrelated protein 1 and Wnt inhibitory factor 1-on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia. Response to tyrosine kinase inhibitors was analyzed in secreted frizzled-related protein 1 and Wnt inhibitory factor 1 stably transfected K562 cells. Experiments were repeated using a tetracycline-inducible expression system, confirming previous results. In addition, response to tyrosine kinase inhibitor treatment was also analyzed using the secreted frizzled-related protein 1 expressing, BCR-ABL positive MEG01 cell line, in the presence and absence of a secreted frizzled-related protein 1 inhibitor. Our data suggests that total cellular β-catenin levels decrease in the presence of secreted frizzled-related protein 1 and Wnt inhibitory factor 1, and a significant increase in cell death after tyrosine kinase inhibitor treatment is observed. On the contrary, when secreted frizzled-related protein 1 is suppressed, total β-catenin levels increase in the cell and the cells become resistant to tyrosine kinase inhibitors. We suggest that Wnt antagonists carry the potential to be exploited in designing new agents and strategies for the advanced and resistant forms of chronic myeloid leukemia.

show abstract

Targeting Leukemia Stem Cells: Which Pathways Drive Self-Renewal Activity in T-Cell Acute Lymphoblastic Leukemia?

Cited by 20 publications

References 79 publications

Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells

Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells

TThe role of hypoxia-inducible factors in leukemias

Forced expression of Wnt antagonists sFRP1 and WIF1 sensitizes chronic myeloid leukemia cells to tyrosine kinase inhibitors

Contact Info

Product

Resources

About