CD95 (FAS/APO-1) Antigen is a New Prognostic Marker of Blast Cells of Acute Lymphoblastic Leukaemia Patients

Baryshnikov, A. Yu.; Polosukhina, E. R.; Tupitsin, N. N.; Gavrikova, N. V.; Andreeva, Ludmila; Заботина, Т. Н.; Mayakova, S. A.; Kurmashov, V I; Syrkin, A. B.; Кадагидзе, З. Г.; Blochin, D. Yu.; Shishkin, Yu. V.

doi:10.1007/978-1-4615-4811-9_27

Cited by 22 publications

(8 citation statements)

References 6 publications

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“…85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 This is likely owing to the fact that CD95 is often downregulated during tumor progression because cancer cells need to lower the risk of undergoing apoptosis while benefiting from CD95's tumorigenic activities. Occasionally, CD95L was also described as a positive prognostic marker for cancer.…”

Section: Other Activities Of the Apoptosis-inducing Receptor Cd95mentioning

confidence: 99%

The role of CD95 and CD95 ligand in cancer

et al. 2015

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CD95 (Fas/APO-1) and its ligand, CD95L, have long been viewed as a death receptor/death ligand system that mediates apoptosis induction to maintain immune homeostasis. In addition, these molecules are important in the immune elimination of virus-infected cells and cancer cells. CD95L was, therefore, considered to be useful for cancer therapy. However, major side effects have precluded its systemic use. During the last 10 years, it has been recognized that CD95 and CD95L have multiple cancer-relevant nonapoptotic and tumor-promoting activities. CD95 and CD95L were discovered to be critical survival factors for cancer cells, and were found to protect and promote cancer stem cells. We now discuss five different ways in which inhibiting or eliminating CD95L, rather than augmenting, may be beneficial for cancer therapy alone or in combination with standard chemotherapy or immune therapy.

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Section: Other Activities Of the Apoptosis-inducing Receptor Cd95mentioning

confidence: 99%

The role of CD95 and CD95 ligand in cancer

et al. 2015

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“…In our study, the ALL patients had low levels of FAS at diagnosis, followed by a significant increase at disease remission. In some pediatric ALL studies, increased levels of FAS have been associated with longer survival in complete remission (Baryshnikov et al ., 1999), whereas other studies found no association of FAS levels with outcome (Wuchter et al ., 2000; Aref et al ., 2004; Fulda, 2009). At this time, we suggest that increased FAS levels at remission post induction treatment could discriminate patients who are not resistant to chemotherapy, but additional studies with long-term follow-up are needed to further address this issue.…”

Section: Discussionmentioning

confidence: 99%

Enhanced levels of the apoptotic BAX/BCL-2 ratio in children with acute lymphoblastic leukemia and high-risk features

et al. 2013

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It has been suggested that leukemia is characterized by an impaired balance between the proliferation of blood cells and their capacity to undergo apoptosis. The aim of this study was to examine the expression of key molecules related to apoptosis (BCL-2, BAX, FAS, FAS-L) in children with acute lymphoblastic leukemia (ALL). Measurement of BCL-2 and BAX mRNA was performed by quantitative real-time PCR, and membrane expression of FAS and FAS-L was assessed by flow cytometry in bone marrow mononuclear cells, both at diagnosis and at remission following induction chemotherapy. At diagnosis, increased levels of the apoptotic BAX/BCL-2 ratio were observed in children older than 10 years and with higher white blood cell counts. A DNA index < 1.16 was associated with increased BAX/BCL-2, both at diagnosis and at remission, and the del(9p) chromosome abnormality with increased BAX/BCL-2 at remission. The expression of the apoptotic receptor FAS was significantly higher at remission compared to diagnosis, which might reflect enhanced sensitivity of the leukemic clone to apoptosis and response to treatment. Altogether, our results highlight the association of apoptosis-related genes with clinical and cytogenetic prognostic parameters in pediatric ALL. A better understanding of the mechanisms and regulation of apoptosis should enable the design of novel targeted therapies for these patients.

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“…Using an unsupervised approach, we found that the expression of 140 genes was increased, and was repressed in 489 genes in leukemic Klf5 Δ/Δ B-cell precursors (Figure 3A ; Supplementary Data ). Deletion of Klf5 influenced the expression of B-lineage survival genes including survivin ( Birc5 ) [ 36 ], Fas [ 37 , 38 ], Tnfsf10 [ 39 ], Irf7 [ 40 ] and Casp4 [ 41 ] ( Supplementary Figure 4A–4E ). The Ikzf1, Cbx5, Hmgb3, Ebf1 and Pax5 genes, all of which have been implicated in B-cell differentiation and associated with the progression of BCR-ABL1 B-ALL, were not affected by the loss of Klf5 in leukemic B-cell precursors ( Supplementary Figure 4F–4J ).…”

Section: Resultsmentioning

confidence: 99%

KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia

et al. 2018

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High-risk B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge despite advances in the use of tyrosine kinase inhibitors and chimeric-antigen-receptor engineered T cells. Lymphoblastic-leukemia precursors are highly sensitive to oxidative stress. KLF5 is a member of the Krüppel-like family of transcription factors. KLF5 expression is repressed in B-ALL, including BCR-ABL1+ B-ALL. Here, we demonstrate that forced expression of KLF5 in B-ALL cells bypasses the imatinib resistance which is not associated with mutations of BCR-ABL. Expression of Klf5 impaired leukemogenic activity of BCR-ABL1+ B-cell precursors in vitro and in vivo. The complete genetic loss of Klf5 reduced oxidative stress, increased regeneration of reduced glutathione and decreased apoptosis of leukemic precursors. Klf5 regulation of glutathione levels was mediated by its regulation of glutathione-S-transferase Mu 1 (Gstm1), an important regulator of glutathione-mediated detoxification and protein glutathionylation. Expression of Klf5 or the direct Klf5 target gene Gstm1 inhibited clonogenic activity of Klf5∆/∆ leukemic B-cell precursors and unveiled a Klf5-dependent regulatory loop in glutamine-dependent glutathione metabolism. In summary, we describe a novel mechanism of Klf5 B-ALL suppressor activity through its direct role on the metabolism of antioxidant glutathione levels, a crucial positive regulator of leukemic precursor survival.

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CD95 (FAS/APO-1) Antigen is a New Prognostic Marker of Blast Cells of Acute Lymphoblastic Leukaemia Patients

Cited by 22 publications

References 6 publications

The role of CD95 and CD95 ligand in cancer

The role of CD95 and CD95 ligand in cancer

Enhanced levels of the apoptotic BAX/BCL-2 ratio in children with acute lymphoblastic leukemia and high-risk features

KLF5 controls glutathione metabolism to suppress p190-BCR-ABL+ B-cell lymphoblastic leukemia

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