scholarly journals Role of CD135/CD117 on Prognosis and Overall Survival of Acute Myeloid Leukemia

2019 ◽  
Vol 20 (9) ◽  
pp. 2625-2631
Author(s):  
Mortaza Raeisi ◽  
Ali Reza Nikhanfar ◽  
Babak Nejate ◽  
Ali Akabr Movassaghpour Akbari ◽  
Roya Dolatkhah ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Li ◽  
Zheng Ge
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Cell Function ◽  
Adverse Outcomes ◽  
High Expression ◽  
Micro Rnas ◽  
Acute Myeloid

Abstract Background Acute myeloid leukemia (AML) remains one of the most common hematological malignancies, posing a serious challenge to human health. HSPA8 is a chaperone protein that facilitates proper protein folding. It contributes to various activities of cell function and also is associated with various types of cancers. To date, the role of HSPA8 in AML is still undetermined. Methods In this study, public datasets available from the TCGA (Cancer Genome Atlas) and GEO (Gene Expression Omnibus) were mined to discover the association between the expression of HSPA8 and clinical phenotypes of CN-AML. A series of bioinformatics analysis methods, including functional annotation and miRNA-mRNA regulation network analysis, were employed to investigate the role of HSPA8 in CN-AML. Results HSPA8 was highly expressed in the AML patients compared to the healthy controls. The high HSPA8 expression had lower overall survival (OS) rate than those with low HSPA8 expression. High expression of HSPA8 was also an independent prognostic factor for overall survival (OS) of CN-AML patients by multivariate analysis. The differential expressed genes (DEGs) associated with HSPA8 high expression were identified, and they were enriched PI3k-Akt signaling, cAMP signaling, calcium signaling pathway. HSPA8 high expression was also positively associated with micro-RNAs (hsa-mir-1269a, hsa-mir-508-3p, hsa-mir-203a), the micro-RNAs targeted genes (VSTM4, RHOB, HOBX7) and key known oncogenes (KLF5, RAN, and IDH1), and negatively associated with tumor suppressors (KLF12, PRKG1, TRPS1, NOTCH1, RORA). Conclusions Our research revealed HSPA8 as a novel potential prognostic factor to predict the survival of CN-AML patients. Our data also revealed the possible carcinogenic mechanism and the complicated microRNA-mRNA network associated with the HSPA8 high expression in AML.

scholarly journals Role of new Immunophenotypic Markers on Prognostic and Overall Survival of Acute Myeloid Leukemia: a Systematic Review and Meta-Analysis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
A. F. O. Costa ◽  
D. L. Menezes ◽  
L. H. S. Pinheiro ◽  
A. F. Sandes ◽  
M. A. P. Nunes ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Meta Analysis ◽  
Acute Myeloid

Limitations of Performance Status (PS) Assignment in Predicting Outcomes of Acute Myeloid Leukemia (AML) and the Role of Objective Parameters in Predicting PS Assignment,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4191-4191
Author(s):  
Kathleen Wren Phelan ◽  
Sucha Nand ◽  
Laura C Michaelis
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Performance Status ◽  
Albumin Level ◽  
Clinical Parameters ◽  
The Relationship ◽  
Acute Myeloid

Abstract Abstract 4191 Background: Performance status is traditionally used to judge fitness in cancer patients. It is often a key factor in determining appropriateness for chemotherapy and entry into clinical trials. Most research on PS has been in solid tumor patients, but it is generally assumed to be valid in hematologic malignancies as well. However, PS assessment can be problematic, especially in patients who have become ill quickly or where there are conflicting parameters; e.g. patients whose function is limited but who are still actively working. We explored the role of PS in patients with AML to determine if alternative, more objectively determined parameters, could predict PS. We evaluated the relationship between PS and rates of complete remission (CR) and duration of overall survival (OS) as well as the relationship between objectively determined pretreatment parameters and these outcomes. Methods: Approval for retrospective data collection was obtained by the institutional IRB. A randomly selected cohort of 145 patients with newly diagnosed AML was identified using pharmacy records of treatment with induction agents cytarabine, daunorubicin or azacitidine. We excluded patients with acute promyelocytic leukemia. Pretreatment data was collected from the electronic medical record of each subject, including AML subtype, age, gender, PS, presence of infection at diagnosis, peripheral blood white blood cell count, peripheral blood blast percentage, hemoglobin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, creatinine, albumin, left ventricular ejection fraction (LVEF), bone marrow cellularity, bone marrow blast percentage and cytogenetics. Achievement of complete remission was assessed and overall survival was calculated in months from diagnosis to either death or date of censorship. PS was obtained from physician notes and documented as a Zubrod score. In the absence of documentation, the authors reviewed medical records for presenting symptoms, mobility and functional status and made an assignment. Retrospective assignment of PS was reviewed and confirmed by at least two of the authors. Logistic regression was performed to examine the relationship between pretreatment characteristics and CR, and the effect of pretreatment characteristics and the assignment of PS, dichotomized as good (0–1) vs. poor (2–4). Linear regression analysis was used to investigate the relationship between pretreatment characteristics and OS. Results: A total of 120/145 (83%) were assigned a PS of 0, 1. Twenty patients were considered to have a PS of 2 and five patients had a PS of 3. There was a statistically significant relationship between a good PS assignment and a higher albumin level (OR 5.32, p=0.000, 95% CI 2.32, 12.22). There was no significant relationship between the remaining clinical parameters and PS assignment, including age at diagnosis. Ninety-three patients (64%) achieved a CR. There was no relationship between PS, assigned either contemporarily or retrospectively, with the achievement of CR. The median overall survival was 15 months (range 0 to 92 months). PS did not predict the duration of OS. As is well reported, CR was significantly more likely in younger (< 60 yrs) patients and patients with favorable cytogenetics. Median OS was also prolonged in these patients. No additional pretreatment characteristics were significantly related to CR or OS except LVEF. Patients with an LVEF greater than 50% were more likely to achieve a CR (P=0.0001) and had a longer OS. Conclusions: We found that, among pretreatment characteristics, a higher albumin level was associated with a good performance status. Age was not a predictor of PS. Contrary to expectations, in this population of treated AML patients, PS did not predict either CR or OS. In addition to the association of younger age and favorable cytogenetics with better outcomes, we found that a higher LVEF is also associated with higher CR rates, but this is likely explained by choice of chemotherapeutic agents. Our data calls into question the use of PS as a tool to guide therapy in routine clinical management of acute myeloid leukemia. Prospective studies should evaluate the utility of more objective and more reliably documented clinical parameters than PS for predicting patient outcome. Disclosures: No relevant conflicts of interest to declare.

Association of HLA-G Haplotype Risk Model with Overall Survival In Acute Myeloid Leukemia Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2169-2169
Author(s):  
Anja Volbracht ◽  
Juergen R Novotny ◽  
Crista Ochsenfarth ◽  
Magdalena Switala ◽  
Ulrich Frey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Tumor Escape ◽  
Tumor Immune Escape ◽  
Group A ◽  
Group B ◽  
Acute Myeloid

Abstract Abstract 2169 Introduction: The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and exerts multiple immunosuppressive functions. Thus, HLA-G expression in tumor cells favors tumor immune escape and tumor progression. The HLA-G gene polymorphism is extremely restricted in comparison to the classical HLA antigens. However, specific HLA-G polymorphisms in exons 3, 4, 5, 7 and parts of the 3′UTR encode for different haplotypes/alleles. Because of the prognostic role of HLA-G in cancer, especially in B-CLL, we investigated here the role of the HLA-G haplotypes in acute myeloid leukemia (AML). Methods: Genotyping was performed on the basis of examining exons 3, 4, 5, 7 and parts of the 3′UTR by pyrosequencing in 166 patients with AML. In total, we found 17 different haplotypes in the cohort. Results: The haplotype distributions between 166 AML patients and 190 healthy controls were significantly different in two alleles, arguing that these two haplotypes of HLA-G on the one hand increases (*01:06, p=0.042) and on the other hand decreases (*01:01:12 variante, p=0.0014) the susceptibility for AML. Next a risk model was generated for overall survival (OS) adapted to specific haplotypes/alleles of the HLA-G gene. The favorable group (A) consisted of the alleles *01:06 and *01:01:20 variant at codon 57 G (12 patients), the intermediate group (B) of *01:01:20, *01:04:10, *01:01:30 and *01:01:41 variant at codon 57 A (113 patients) and the unfavorable group (C) of the remaining 11 alleles (41 patients). The OS for patients in group C was significantly (p=0.02) shorter (median OS 613 days) than for those in group B (median OS 961 days) and A (median OS not reached). Multivariate analysis shows a trend that the risk HLA-G model (Hazard ratio (HR) 1.4, p=0.084) was an independent predictor next to the established prognostic factors cytogenetics (HR 2.1, p=0.001), age (HR 1.8, p=0.009), leucocytes (HR 1.6, p=0.026), ECOG stage (HR 1.5, p=0.006) and platelets (HR 2.1, p=0.015). Moreover, the new risk model was able to further subdivide patients with intermediate cytogenetic risk profile (median OS: group A not reached; group B 987 days; group C 624 days; p=0.10). Conclusion: Our study is the first study demonstrating that the combination of different alleles of the HLA-G gene is associated with the overall survival in AML patients. This fact emphasizes the extensive role of this gene by the tumor escape mechanism and could be responsible for progress in other cancers. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of the Slit-Robo Family in Adult Patients with Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3816-3816
Author(s):  
Aleksandra Golos ◽  
Dorota Jesionek-Kupnicka ◽  
Tadeusz Robak ◽  
Ewa Wawrzyniak ◽  
Lidia Anna Gil ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Involvement ◽  
Control Group ◽  
Newly Diagnosed ◽  
Low Expression ◽  
Acute Myeloid

Abstract Introduction: SLIT-ROBO is newly discovered ligand-receptor family of neuronal guidance molecules. Recently, it has been proved that these proteins are involved in both, physiologic and pathologic angiogenesis. In animal models, it was shown both, pro-and antiangiogenic of SLIT-ROBO signaling. Moreover, the interaction of SLIT ligands with their roundabout receptors (ROBO) results in promotion of apoptosis, adhesion and blocking of cell cycle. There is evidence that SLIT-ROBO proteins are involved in pathogenesis of solid tumors, both in angiogenesis dependent and independent way. The role of SLIT-ROBO proteins in biology of acute myeloid leukemia (AML) remains unknown.The only two hitherto published studies considering ROBO4 expression in AML have revealed its increased expression in the blasts cells. The aim of the study was to evaluate the role of SLIT-ROBO proteins in AML. The expression of SLIT ligands, and their receptors ROBO was assessed in bone marrow of newly diagnosed AML patients and in the control group. The expression level of the proteins was correlated with known prognostic factors, response to treatment and overall survival (OS), as well as angiogenesis activity. To our knowledge, it has been the first study investigating the whole family of SLIT-ROBO proteins in AML. Methods: Expression SLIT-ROBO proteins was assessed in bone marrow biopsy specimens of 79 newly diagnosed AML patients with median age 59 years [18-87]. The paraffin-embedded tissue blocks were retrieved and subjected to immunohistochemistry for SLIT ligands (SLIT1, SLIT2, SLIT3), and their receptors ROBO1, ROBO2, ROBO3, and ROBO4. The positive blasts cells were semi-quantitatively analyzed according to previously published methods (Perrone et al, 2006). For the purpose of analysis the patients were divided into "low-expressers" and "high-expressers". Concurrently, all samples were immunostained for CD34 to calculate microvessel density (MVD) as an equivalent of angiogenesis. The control group was composed of 23 BM biopsies form patients with newly diagnosed lymphoma without bone marrow involvement. Results: Expression of ROBO receptors and SLIT ligands in AML patients and in the control group. In our study higher expression of ROBO1, ROBO2, and ROBO3 was observed more often in AML patients compared to the control group (p<0.0001, p<0.001, and p=0.09, respectively, Fig 1.). In contrast, low expression of SLIT1, SLIT2, and SLIT3 ligands has been shown more often in AML than in control BM samples (p<0.0001, p=0.003, and p=0.001, respectively,Fig.2.). Higher expression of ROBO1, ROBO2, and ROBO3 was more often in AML patients ≥60 years (p=0.04, p=0.008, and p=0.02, respectively).Conversely, low expression of ROBO4 was more often observed in elderly AML (p=0.06). The majority of patients with de novo AML had low expression of SLIT1 and SLIT2 (p=0.053 and p=0.055, respectively). As to ROBO, higher expression of ROBO2 in the group with secondary AML was more frequent (p=0.09). No significant correlations between the SLIT-ROBO proteins' expression,neither cytogenetic risk group nor clinical stage parameters such as WBC, hemoglobin level, proportion of leukemic blasts in BM, or LDH activity were found. Similarly, neither of the SLIT-ROBO proteins influenced the complete remission rate (CR) and overall survival (OS). Relationship between SLIT-ROBO expression and angiogenesis activity in AML patients and control group. Significantly higher MVD in BM of AML patients than in control group (Me 51 [9-140] vs 16 [4-78], p<0.0001) has been observed. ROBO4was the only protein that expression correlated significantly with MVD. Higher expression of ROBO4 was associated with higher MVD in both, AML and the control group (p=0.05 and p=0.01, respectively). Conclusions: SLIT-ROBO family members play a role in biology of AML. ROBO4 is involved in both, physiologic and pathologic angiogenesis A better understanding of SLIT-ROBO signaling pathway in leukemic blasts may create new optionsfor AML therapy. Acknowledgments: AG and DJ-K both equally contributed to the study. This work was supported by grants from Medical University of Lodz, Lodz, Poland (502-03/1-093-01/502-14-077 and 503/1-093-01/503-11-001). Disclosures Robak: Eisai Inc: Research Funding. Wierzbowska:Janssen, Celgene: Consultancy.

High Levels of Soluble HLA-I in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome: Relevance to Clinical Behavior and b2M Levels.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1070-1070
Author(s):  
Maher Albitar ◽  
Marcy Johnson ◽  
Kim-Ann Do ◽  
Amanda Day ◽  
Iman Jilani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Tumor Marker ◽  
Myeloid Leukemia ◽  
Response To Therapy ◽  
Beta Chain ◽  
Clinical Behavior ◽  
Soluble Hla ◽  
Acute Myeloid

Abstract Human leukocyte antigen-class I (HLA-I) molecules are membrane-associated proteins that contain two separate polypeptide chains: an alpha heavy chain and a beta chain. The beta chain is the b-2 microglobulin (b2-M). Significant levels of free soluble HLA-I (sHLA-I) have been detected in serum and studied as a marker for immunomodulation in patients with infection and after transplant. Little is known about the role of sHLA-I as a tumor marker, despite the documentation of b2-M as a tumor marker. We measured the levels of sHLA-I and b2-M in the plasma of 205 patients with acute myeloid leukemia (AML) and 95 patients with myelodysplastic syndrome (MDS) and assessed the value of both markers in predicting clinical behavior. Both sHLA-I and b2-M were strong predictors of response to therapy (P = 0.03 and P = 0.001, respectively), overall survival (both P &lt;0.0001), and remission duration (both P &lt;0.001). The Multivariate Cox proportional hazards model incorporating cytogenetics, b2-M, and sHLA-I demonstrated that only b2-M was an independent predictor of survival. In patients with MDS, b2-M but not sHLA-I correlated with response to therapy, overall survival, and response duration. These data not only establish the role of sHLA-I as a tumor marker in AML, but also suggest that MDS disease is significantly different from AML. Because sHLA-I has been reported to be an immunomodulator that inhibits the cytotoxic effects of T-lymphocytes, its role as an immunomodulator in patients with MDS needs further investigation. Figure Figure

Role of FLT3 gene mutations in acute myeloid leukemia: effect on course of disease and results of therapy

2019 ◽  
Vol XIV (1) ◽  
Author(s):  
A.M. Radzhabova ◽  
S.V. Voloshin ◽  
I.S. Martynkevich ◽  
A.A. Kuzyaeva ◽  
V.A. Shuvaev ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Course Of Disease ◽  
Acute Myeloid

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

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