scholarly journals Induction of the proapoptotic tumor suppressor gene Cell Adhesion Molecule 1 by chemotherapeutic agents is repressed in therapy resistant acute myeloid leukemia

2014 ◽  
Vol 54 (12) ◽  
pp. 1815-1819 ◽  
Author(s):  
Muriel C. Fisser ◽  
Anna Rommer ◽  
Katarina Steinleitner ◽  
Gerwin Heller ◽  
Friederike Herbst ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Adhesion ◽  
Tumor Suppressor ◽  
Adhesion Molecule ◽  
Myeloid Leukemia ◽  
Cell Adhesion Molecule ◽  
Suppressor Gene ◽  
Chemotherapeutic Agents ◽  
Cell Adhesion Molecule 1 ◽  
Acute Myeloid

scholarly journals Expression of the Neural Cell Adhesion Molecule CD56 Is Associated With Short Remission Duration and Survival in Acute Myeloid Leukemia With t(8; 21)(q22; q22)

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1643-1648 ◽  
Author(s):  
Maria R. Baer ◽  
Carleton C. Stewart ◽  
David Lawrence ◽  
Diane C. Arthur ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Treatment Outcome ◽  
Cell Adhesion ◽  
Myeloid Leukemia ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell Adhesion ◽  
Cd56 Expression ◽  
Acute Myeloid

Abstract Although acute myeloid leukemia (AML) with t(8; 21) (q22; q22) is associated with a high complete remission (CR) rate and prolonged disease-free survival, treatment outcome is not universally favorable. Identifying factors that predict for treatment outcome might allow therapy to be optimized based on risk. AML with t(8; 21) has a distinctive immunophenotype, characterized by expression of the myeloid and stem cell antigens CD13, CD15, CD34, and HLADr, and frequent expression of the B-cell antigen CD19 and the neural cell adhesion molecule CD56, a natural killer cell/stem cell antigen. Because CD56 expression has been associated with both extramedullary leukemia and multidrug resistance, we sought to correlate CD56 expression with treatment outcome in AML with t(8; 21). Pretreatment leukemia cells from 29 adult de novo AML patients with t(8; 21) treated on Cancer and Leukemia Group B (CALGB) protocols were immunophenotyped by multiparameter flow cytometry as part of a prospective immunophenotyping study of adult AML (CALGB 8361). CD56 was expressed in 16 cases (55%). There was no correlation between CD56 expression and age, sex, white blood cell count, granulocyte count, the presence of additional cytogenetic abnormalities, or the presence of extramedullary disease at diagnosis. The CR rate to standard-dose cytarabine and daunorubicin was similar for cases with and without CD56 expression (88% v 92%; P = 1.0). Post-CR therapy included at least one course of high-dose cytarabine in 24 of 26 patients who achieved CR; numbers of courses administered were similar in cases with and without CD56 expression. Although post-CR therapy did not differ, CR duration was significantly shorter in cases with CD56 expression compared with those without (median, 8.7 months v not reached; P = .01), as was survival (median, 16.5 months v not reached; P = .008). We conclude that CD56 expression in AML with t(8; 21) is associated with significantly shorter CR duration and survival. Our results suggest that CD56 expression may be useful in stratifying therapy for this subtype of AML.

scholarly journals Expression of the Neural Cell Adhesion Molecule CD56 Is Associated With Short Remission Duration and Survival in Acute Myeloid Leukemia With t(8; 21)(q22; q22)

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1643-1648 ◽  
Author(s):  
Maria R. Baer ◽  
Carleton C. Stewart ◽  
David Lawrence ◽  
Diane C. Arthur ◽  
John C. Byrd ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Treatment Outcome ◽  
Cell Adhesion ◽  
Myeloid Leukemia ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell Adhesion ◽  
Cd56 Expression ◽  
Acute Myeloid

Although acute myeloid leukemia (AML) with t(8; 21) (q22; q22) is associated with a high complete remission (CR) rate and prolonged disease-free survival, treatment outcome is not universally favorable. Identifying factors that predict for treatment outcome might allow therapy to be optimized based on risk. AML with t(8; 21) has a distinctive immunophenotype, characterized by expression of the myeloid and stem cell antigens CD13, CD15, CD34, and HLADr, and frequent expression of the B-cell antigen CD19 and the neural cell adhesion molecule CD56, a natural killer cell/stem cell antigen. Because CD56 expression has been associated with both extramedullary leukemia and multidrug resistance, we sought to correlate CD56 expression with treatment outcome in AML with t(8; 21). Pretreatment leukemia cells from 29 adult de novo AML patients with t(8; 21) treated on Cancer and Leukemia Group B (CALGB) protocols were immunophenotyped by multiparameter flow cytometry as part of a prospective immunophenotyping study of adult AML (CALGB 8361). CD56 was expressed in 16 cases (55%). There was no correlation between CD56 expression and age, sex, white blood cell count, granulocyte count, the presence of additional cytogenetic abnormalities, or the presence of extramedullary disease at diagnosis. The CR rate to standard-dose cytarabine and daunorubicin was similar for cases with and without CD56 expression (88% v 92%; P = 1.0). Post-CR therapy included at least one course of high-dose cytarabine in 24 of 26 patients who achieved CR; numbers of courses administered were similar in cases with and without CD56 expression. Although post-CR therapy did not differ, CR duration was significantly shorter in cases with CD56 expression compared with those without (median, 8.7 months v not reached; P = .01), as was survival (median, 16.5 months v not reached; P = .008). We conclude that CD56 expression in AML with t(8; 21) is associated with significantly shorter CR duration and survival. Our results suggest that CD56 expression may be useful in stratifying therapy for this subtype of AML.

scholarly journals DNA hypermethylation and epigenetic silencing of the tumor suppressor gene, SLC5A8, in acute myeloid leukemia with the MLL partial tandem duplication

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 2013-2016 ◽  
Author(s):  
Susan P. Whitman ◽  
Björn Hackanson ◽  
Sandya Liyanarachchi ◽  
Shujun Liu ◽  
Laura J. Rush ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Suppressor Gene ◽  
Dna Hypermethylation ◽  
Partial Tandem Duplication ◽  
Acute Myeloid

Abstract Posttranslationally modified histones and DNA hypermethylation frequently interplay to deregulate gene expression in cancer. We report that acute myeloid leukemia (AML) with an aberrant histone methyltransferase, the mixed lineage leukemia partial tandem duplication (MLL-PTD), exhibits increased global DNA methylation versus AML with MLL-wildtype (MLL-WT; P = .02). Among the differentially methylated genes, the SLC5A8 tumor suppressor gene (TSG) was more frequently hypermethylated (P = .003). In MLL-PTD+ cell lines having SLC5A8 promoter hypermethylation, incubation with decitabine activated SLC5A8 expression. Ectopic SLC5A8 expression enhanced histones H3 and H4 acetylation in response to the histone deacetylase inhibitor, valproate, consistent with the encoded protein—SMCT1—short-chain fatty acid transport function. In addition, enhanced cell death was observed in SMCT1-expressing MLL-PTD+ AML cells treated with valproate. Within the majority of MLL-PTD AML is a mechanism in which DNA hypermethylation silences a TSG that, together with MLL-PTD, can contribute further to aberrant chromatin remodeling and altered gene expression.

scholarly journals Polymerase chain reaction-based diagnosis of del (5q) in acute myeloid leukemia and myelodysplastic syndrome identifies a minimal deletion interval

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2665-2670 ◽  
Author(s):  
SK Horrigan ◽  
CA Westbrook ◽  
AH Kim ◽  
M Banerjee ◽  
W Stock ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Myeloid Leukemia ◽  
Suppressor Gene ◽  
Malignant Cells ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Acute Myeloid

Loss of all or part of the long arm of human chromosome 5 is a recurrent abnormality in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), especially after chemotherapy for a prior malignancy. It is one of the worst prognostic indicators in AML, associated with chemotherapy resistance and short survival. These deletions center at band 5q31, which has thus been proposed as the location of a tumor suppressor gene; this site is to be distinguished from that observed in 5q- syndrome, centering at 5q32. To define the molecular extent and the clinical prevalence of 5q31 deletions, we collected a series of AML and MDS cases of mixed karyotype, taking care to exclude MDS cases with 5q- syndrome. The samples were analyzed for loss of heterozygosity (LOH) using a panel polymerase chain reaction (PCR)-based microsatellite markers from 5q, comparing malignant cells with normal tissue derived from lymphoblastoid cell lines or buccal mucosa scrapings. Losses were detected in seven of 29 matched samples, including four of 17 with MDS, and three of 12 with AML; six of these seven also had a cytogenetically-visible del(5q) or -5. The one case without a cytogenetic deletion showed molecular loss of three contiguous markers, with retention of flanking markers interleukin-9 (IL-9) and D5S414, and thus contained a small deletion that is below cytogenetic resolution. PCR failed to detect 5q loss in two cases with large cytogenetic deletions, but both had been treated and contained low percentages of malignant cells in the samples. This study thus led to the identification of a case with a minimal deletion for the 5q31 tumor suppressor gene, specified by IL-9-D5S414, that is approximately 1 Mb (2 cM) in extent. Additionally, we demonstrate that PCR-based allelotyping is a reliable method for the detection of chromosomal deletion in myeloid malignancy, providing the specimens contain a high proportion of malignant cells. These studies will help to identify the tumor-suppressor gene at 5q31, and will help to develop molecular methods for diagnosis and monitoring of these disorders.

The C/EBPδ tumor suppressor is silenced by hypermethylation in acute myeloid leukemia

Blood ◽  
2007 ◽  
Vol 109 (9) ◽  
pp. 3895-3905 ◽  
Author(s):  
Shuchi Agrawal ◽  
Wolf-Karsten Hofmann ◽  
Nicola Tidow ◽  
Mathias Ehrich ◽  
Dirk van den Boom ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Transcriptional Repression ◽  
Myeloid Leukemia ◽  
Leukemic Cell ◽  
Suppressor Gene ◽  
Primary Diagnosis ◽  
Molecular Alteration ◽  
Acute Myeloid

Abstract Aberrant DNA methylation is the most frequent molecular alteration in acute myeloid leukemia (AML). To identify methylation-silenced genes in AML, we performed microarray analyses in U937 cells exposed to the demethylating agent 5-aza-deoxy-cytidine. Overall, 274 transcripts were significantly induced. Interestingly, C/EBPδ expression was significantly induced (more than 10-fold) by demethylation whereas expression of all other C/EBP family members remained unchanged. The C/EBPδ promoter was strongly methylated in different leukemic cell lines and showed signs of a repressed chromatin state. Analyses of the promoter regions of the entire C/EBP family (α, β, γ, δ, ϵ, ζ) in bone marrow samples from AML patients (n = 80) and controls (n = 15) by mass spectrometry revealed that C/EBPδ is the most commonly hypermethylated C/EBP gene in AML. Hypermethylation occurred in more than 35% of AML patients at primary diagnosis. A significant correlation (P = .016) was observed between hypermethylation of the C/EBPδ promoter and low expression of C/EBPδ in AML patients. C/EBPδ promoter activity was strongly repressed by methylation in vitro, and transcriptional repression partially depended on MeCP2 activity. C/EBPδ exhibited growth-inhibitory properties in primary progenitor cells as well as in Flt3-ITD–transformed cells. Taken together, C/EBPδ is a novel tumor suppressor gene in AML that is silenced by promoter methylation.

scholarly journals Association between methylation of tumor suppressor gene SOCS1 and acute myeloid leukemia

2018 ◽  
Author(s):  
Xiao‑Hui Zhang ◽  
Lin Yang ◽  
Xiao‑Jun Liu ◽  
Ying Zhan ◽  
Yu‑Xia Pan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Myeloid Leukemia ◽  
Suppressor Gene ◽  
Acute Myeloid
Sign in / Sign up

Export Citation Format

Share Document