NEDD9, an independent good prognostic factor in intermediate-risk acute myeloid leukemia patients

Abstract Splicing factor (SF) mutations are important contributors to the pathogenesis of hematological malignancies; however, their relevance in risk classification of acute myeloid leukemia (AML) warrants further investigation. To gain more insight into the characteristics of patients with AML carrying SF mutations, we studied their association with clinical features, cytogenetic and molecular abnormalities, and clinical outcome in a large cohort of 1447 patients with AML and high-risk myelodysplastic syndrome. SF mutations were identified in 22% of patients and were associated with multiple unfavorable clinical features, such as older age, antecedent myeloid disorders, and adverse risk factors (mutations in RUNX1 and ASXL1). Furthermore, they had significantly shorter event-free and overall survival. Notably, in European LeukemiaNet (ELN) 2017 favorable- and intermediate-risk groups, SF3B1 mutations were indicative of relatively poor prognosis. In addition, patients carrying concomitant SF mutations and RUNX1 mutations had a particularly adverse prognosis. In patients without any of the 4 most common SF mutations, RUNX1 mutations were associated with relatively good outcome, which was comparable to that of intermediate-risk patients. In this study, we propose that SF mutations be considered for incorporation into prognostic classification systems. First, SF3B1 mutations could be considered an intermediate prognostic factor when co-occurring with favorable risk features and as an adverse prognostic factor for patients currently categorized as having intermediate risk, according to the ELN 2017 classification. Second, the prognostic value of the current adverse factor RUNX1 mutations seems to be limited to its co-occurrence with SF mutations.

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The Presence of FLT3/ITD Mutations Is an Independent Prognostic Factor in Acute Myeloid Leukemia Patients with Normal Karyotype.

Blood ◽

10.1182/blood.v104.11.3008.3008 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3008-3008 ◽

Cited By ~ 1

Author(s):

Yeo-Kyeoung Kim ◽

Je-Jung Lee ◽

Yu-Ra Lee ◽

Il-Kwon Lee ◽

Hee-Nam Kim ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Myeloid Leukemia ◽

Risk Group ◽

Normal Karyotype ◽

Intermediate Risk ◽

Free Survival ◽

Significant Difference ◽

Acute Myeloid

Abstract An internal tandem duplication of the FLT3 gene (FLT3/ITD) has been detected in approximately 20–30% of patients with acute myeloid leukemia (AML). These are frequently associated with poor outcome in AML patients, but it is still a matter of debate whether the FLT3/ITD mutations play a role in the prognosis of AML patients independently or not. We investigated the presence of FLT3/ITD mutation in 165 patients with de novo AML, except acute promyelocytic leukemia (APL), to evaluate its clinical and prognostic significance. The FLT3/ITD mutations were studied on bone marrow samples at diagnosis using PCR assay. Of the patients, 58 patients (35.2%) demonstrated the aberrant FLT3/ITD mutations. The patients with FLT3/ITD had significantly higher WBC counts at presentation compared with patients without FLT3/ITD (52.9 ± 66.9 ×109/L vs. 32.4 ± 41.8 ×109/L, p < 0.05). However, there was no statistically significant difference in age, gender, hemoglobin level, platelet count, percentage of peripheral or bone marrow blasts, or the presence of molecular abnormalities between the patients with FLT3/ITD and the patients without FLT3/ITD. To analyze the response to or outcome of therapy, we evaluated 118 patients who received intensive induction chemotherapy. In univariate analysis, there was no significant difference in complete response rate (p = 0.21), in median duration of overall survival (13.9±3.8 ms. vs. 16.5±0 ms., p = 0.07), or in median duration of leukemic-free survival (LFS) (9.8±3.5 ms. vs. 34.6±17.9 ms., p = 0.09) between the patients with FLT3/ITD and the patients without FLT3/ITD. However, the presence of FLT3/ITD was associated with lower LFS in the patients with a cytogenetically intermediate-risk group (p < 0.05). Furthermore, in multivariate analysis, FLT3/ITD mutations were an independent prognostic factor in LFS in AML patients with normal karyotype (p < 0.05). In conclusion, this study demonstrates that the presence of FLT3/ITD mutations is a significantly poor prognostic factor for leukemic free survival in non-APL patients with a cytogenetically intermediate-risk group, especially normal karyotype.

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TET2 mutation is an unfavorable prognostic factor in acute myeloid leukemia patients with intermediate-risk cytogenetics

Blood ◽

10.1182/blood-2011-02-339747 ◽

2011 ◽

Vol 118 (14) ◽

pp. 3803-3810 ◽

Cited By ~ 176

Author(s):

Wen-Chien Chou ◽

Sheng-Chieh Chou ◽

Chieh-Yu Liu ◽

Chien-Yuan Chen ◽

Hsin-An Hou ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Myeloid Leukemia ◽

Negative Impact ◽

Intermediate Risk ◽

Npm1 Mutation ◽

Disease Evolution ◽

Unfavorable Prognostic Factor ◽

Tet2 Mutation ◽

Acute Myeloid

Abstract The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1+/FLT3-ITD− or CEBPA+). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution.

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BAALC-associated miR-3151 is an Independent Prognostic Factor in Young Patients With Intermediate-Risk Cytogenetic Acute Myeloid Leukemia

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2014.06.043 ◽

2014 ◽

Vol 14 ◽

pp. S122-S123

Author(s):

M. Díaz-Beyá ◽

A. Navarro ◽

M. Pratcorona ◽

S. Brunet ◽

J. Nomdedéu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Myeloid Leukemia ◽

Young Patients ◽

Independent Prognostic Factor ◽

Intermediate Risk ◽

Acute Myeloid

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High expression of CD56 may be associated with favorable overall survival in intermediate-risk acute myeloid leukemia

Hematology ◽

10.1080/16078454.2021.1880734 ◽

2021 ◽

Vol 26 (1) ◽

pp. 210-214

Author(s):

Cunte Chen ◽

Chi Leong Chio ◽

Hui Zeng ◽

Yangqiu Li

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

High Expression ◽

Intermediate Risk ◽

Acute Myeloid

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High HSPA8 expression predicts adverse outcomes of acute myeloid leukemia

BMC Cancer ◽

10.1186/s12885-021-08193-w ◽

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.

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