scholarly journals Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Adriana E. Tron ◽  
Matthew A. Belmonte ◽  
Ammar Adam ◽  
Brian M. Aquila ◽  
Lawrence H. Boise ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Specific Inhibitor ◽  
Acute Myeloid

Association between multiple myeloma and acute myeloid leukemia secondary to myelodysplastic syndrome

2013 ◽  
Vol 71 (5) ◽  
pp. 581-584
Author(s):  
Selim Jennane ◽  
Hicham Eddou ◽  
El Mehdi Mahtat ◽  
Johanna Konopacki ◽  
Bertrand Souleau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Acute Myeloid

Socioeconomic Differences in Patient Survival Are Increasing for Acute Myeloid Leukemia and Multiple Myeloma in Sweden

2009 ◽  
Vol 27 (12) ◽  
pp. 2073-2080 ◽  
Author(s):  
Sigurdur Yngvi Kristinsson ◽  
Åsa Rangert Derolf ◽  
Gustaf Edgren ◽  
Paul W. Dickman ◽  
Magnus Björkholm
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
White Collar ◽  
Blue Collar ◽  
Lower Mortality ◽  
Blue Collar Workers ◽  
White Collar Workers ◽  
The Impact ◽  
Acute Myeloid

Purpose An association between socioeconomic status (SES) and survival in acute myeloid leukemia (AML) and multiple myeloma (MM) has not been established in developed countries. We assessed the impact of SES on survival in two large population-based cohorts of AML and MM patients diagnosed in Sweden 1973 to 2005. Patients and Methods The relative risk of death (all cause and cause specific) in relation to SES was estimated using Cox's proportional hazards regression. We also conducted analyses stratified by calendar periods (1973 to 1979, 1980 to 1989, 1990 to 1999, and 2000 to 2005). Results We identified a total of 9,165 and 14,744 patients with AML and MM, respectively. Overall, higher white-collar workers had a lower mortality than other SES groups for both AML (P = .005) and MM (P < .005). In AML patients, a consistently higher overall mortality was observed in blue-collar workers compared with higher white-collar workers in the last three periods (hazard ratio [HR], 1.26; 95% CI, 1.05 to 1.51; HR, 1.23; 95% CI, 1.05 to 1.45; HR, 1.28; 95% CI, 1.04 to 1.57, respectively). In MM, no difference was observed in the first two calendar periods. However, in 1990 to 1999, self-employed (HR, 1.18; 95% CI, 1.02 to 1.37), blue-collar workers (HR, 1.18; 95% CI, 1.04 to 1.32), and retired (HR, 1.45; 95% CI, 1.16 to 1.80) had a higher mortality compared to higher white-collar workers. In 2000 to 2005, blue-collar workers had a higher mortality (HR, 1.31; 95% CI, 1.07 to 1.60) compared with higher white-collar workers. Conclusion SES was significantly associated with survival in both AML and MM. Most conspicuously, a lower mortality was observed among the highest SES group during more recent calendar periods. Differences in management, comorbidity, and lifestyle, are likely factors to explain these findings.

Soluble CD44 Is Increased in Haematopoietic Stem Cell Grafts of Patients with Acute Myeloid Leukemia, Multiple Myeloma and Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3286-3286
Author(s):  
Daniela S. Krause ◽  
Christopher P. Stowell
Keyword(s):  
Multiple Myeloma ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Clinical Outcome ◽  
Myeloid Leukemia ◽  
Haematopoietic Stem Cell ◽  
Malignant Cells ◽  
Haematological Malignancies ◽  
Soluble Cd44 ◽  
Acute Myeloid

Abstract Autologous haematopoietic stem cell transplantation (autoHSCT) after high dose chemotherapy is a widely used form of therapy for patients with leukemia, lymphoma and multiple myeloma. Malignant cells remaining in the graft, however, may reengraft leading to relapse of the original disease. CD44, a transmembrane glycoprotein, which is overexpressed in many malignancies, including most haematological malignancies, and which plays a role in the engraftment of leukemia-initiating cells, is shed from the surface of malignant cells. In order to establish whether there is a correlation between the amount of CD44 shed from the surface of the malignant cells with the number of contaminating cells remaining in the graft, the engraftment potential of the malignant cell population, or clinical outcome after autoHSCT, we measured soluble CD44 (sCD44) in 86 haematopoietic stem cell grafts from patients with haematological malignancies by enzyme-linked immunosorbent assay (ELISA) and compared the results to sCD44 levels in the HSC grafts from 33 healthy donours. The levels of sCD44 were almost 2fold higher in the grafts of patients with acute myeloid leukemia (AML) (mean: 30,015 ng/ml ± 8524), multiple myeloma (mean: 27,564 ng/ml ± 7,801) and diffuse large B-cell Non-Hodgkin-Lymphomas (mean: 22,539 ng/ml ± 8,382) than in healthy HSC donour grafts (mean: 13,035 ng/ml ± 10,075). As expected, levels of sCD44 were highest in auto HSCT grafts of patients with AML. The majority of patients who achieved a complete remission after autoHSCT had relatively low sCD44 values (mean: 22,610 ng/l ± 7439). Levels of sCD44 were greatest in patients who experienced progressive disease (mean: 28,918 ng/ml ± 10,431), and somewhat less elevated in patients with relapsed disease after auto HSCT (mean: 26,171 ng/ml ± 7616). In addition, patients who had levels of sCD44 <25,500 ng/ml had increased survival (33% at 120 months after autoHSCT versus 18% in patients with sCD44 levels of >25,500 ng/ml). These results argue that the levels of soluble CD44 in an HSC graft could serve as a biomarker for the engraftment potential of contaminating malignant cells in the graft, and may correlate with clinical outcome after autoHSCT. Further, these results raise the possibility that CD44 blocking strategies may be beneficial in autoHSCT.

scholarly journals Epigenetic silencing of UBXN8 contributes to leukemogenesis in t(8;21) acute myeloid leukemia

2021 ◽  
Author(s):  
Erna Yang ◽  
Wei Guan ◽  
Desheng Gong ◽  
Jieying Li ◽  
Caixia Han ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Fusion Protein ◽  
Cell Lines ◽  
Promoter Region ◽  
Myeloid Leukemia ◽  
Specific Inhibitor ◽  
Epigenetic Silencing ◽  
Cycle Arrest ◽  
Acute Myeloid

AbstractThe formation of the RUNX1-RUNX1T1 fusion protein, resulting from the t(8;21) translocation, is considered to be one of the initiating events of t(8;21) acute myeloid leukemia (AML). However, the mechanisms of the oncogenic mechanism of RUNX1-RUNX1T1 remain unclear. In this study, we found that RUNX1-RUNX1T1 triggers the heterochromatic silencing of UBXN8 by recognizing the RUNX1-binding sites and recruiting chromatin-remodeling enzymes to the UBXN8 promoter region. Decitabine, a specific inhibitor of DNA methylation, upregulated the expression of UBXN8 in RUNX1-RUNX1T1+ AML cell lines. Overexpression of UBXN8 inhibited the proliferation and colony-forming ability of and promoted cell cycle arrest in t(8;21) AML cell lines. Enhancing UBXN8 levels can significantly inhibit tumor proliferation and promote the differentiation of RUNX1-RUNX1T1+ cells in vivo. In conclusion, our results indicated that epigenetic silencing of UBXN8 via methylation of its promoter region mediated by the RUNX1-RUNX1T1 fusion protein contributes to the leukemogenesis of t(8;21) AML and that UBXN8 targeting may be a potential therapeutic strategy for t(8;21) AML.

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