Lymphoid enhancer binding factor-1 (LEF1) expression as a prognostic factor in adult acute promyelocytic leukemia

Albano, Francesco; Zagaria, Antonella; Anelli, Luisa; Orsini, Paola; Minervini, Crescenzio Francesco; Impera, Luciana; Casieri, Paola; Coccaro, Nicoletta; Tota, Giuseppina; Brunetti, Claudia; Minervini, Angela; Pastore, Domenico; Carluccio, Paola; Mestice, Anna; Cellamare, Angelo; Specchia, Giorgina

doi:10.18632/oncotarget.1619

Cited by 20 publications

(19 citation statements)

References 49 publications

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“…In present study we found that LEF1 low expression AML patients had higher WBC, BM blast percentages, lower platelets level, also had poor cytogenetic, and carried FLT-3 mutation. In agreement with our results, Metzeler et al, [14] conducted a study on 210 cytogenetically normal (CN)-AML patients, also by Albano et al [21]. Fu et al (2014) showed no signi cant di erence regarding age, WBC, FLT3-ITD mutations between LEF1 expression in 101 AML patients.…”

Section: Discussionsupporting

confidence: 92%

“…LEF1 high /low Gal.3 level patients had a signi cantly longer OS ( = 0.03, Figure 3) and borderline signi cantly better EFS ( = 0.05, Figure 3) than others (Table 5). level is a poor prognostic factor in myelodysplastic syndromes, AML [20], acute promyelocytic leukemia of adult patients [21], and childhood ALL [22]. In present study we found that LEF1 low expression AML patients had higher WBC, BM blast percentages, lower platelets level, also had poor cytogenetic, and carried FLT-3 mutation.…”

Section: Discussionsupporting

confidence: 55%

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Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients

Elbaiomy

Aref

Zaafarany

et al. 2019

Advances in Hematology

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Background. Deregulation of the Wnt signaling pathway had a role in haematological malignancies. Previous studies reported that lymphoid enhancer factor 1 (LEF1) expression and serum Galectin-3 level could affect clinical parameters and outcome in acute myeloid leukemia patients, but as far as we know, no study has addressed their combined effect on AML patients. Aim. We studied the expression of LEF1 by real-time qPCR and measured serum level of Gal.3 by ELISA technique in peripheral blood of 69 AML patients and correlated it with different clinicopathological criteria of patients, response, PFS and OS. Results. We found high expression (LEF1high) was associated with better OS (p=0.02) and EFS (p=0.019) compared to LEF1low, low serum Gal.3 level had better OS (p=0.014) and EFS (p=0.02) compared to high serum Gal.3 level. LEF1high less likely to carry a FLT3-ITD (p=0.047) compared to LEF1low patient, also LEF1high characterized by favorable risk (p=0.02) than LEF1low patients. While patients with higher Gal-3 levels characterized by poor risk (p=0.02) than lower Gal.3 lels, also more likely to carry a FLT3-ITD with borderline significance (p=0.054). Combined LEF1high/Gal.3 low patients had lower baseline blast percentages (p=0.02), favorable risk (p=0.01), less likely to carry FLT3-ITD (p=0.02), higher CR rate (p=0.055), shorter time to CR (0.001) than other groups. Among high Gal.3 level group, LEF1high expression improved OS and EFS (20 and 15 months respectively) vs LEF1low expression (13 and 8 months respectively). Conclusion. We conclude that high LEF1 expression was a favorable prognostic marker which can define AML patient risk and outcome independent from assessing the serum galectin.3 level.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 55%

Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients

Elbaiomy

Aref

Zaafarany

et al. 2019

Advances in Hematology

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“…It also mediates Wnt signaling-induced proliferation increase of pro B cells. LEF1 expression is reported to be involved in leukemic transformation [ 4 ], and associated with poor prognosis in adult B precursor acute lymphoblastic leukemia (ALL) [ 6 ], chronic lymphocytic leukemia(CLL)[ 6 , 7 ], cytogenetically normal acute myeloid leukemia (AML), and adult de novo acute promyelocytic leukemia (APL)[ 8 ]. These reports indicate that LEF1 is involved in the oncogenesis of leukemia.…”

Section: Introductionmentioning

confidence: 99%

Characterization of LEF1 High Expression and Novel Mutations in Adult Acute Lymphoblastic Leukemia

et al. 2015

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Aberrant activation of the Wnt pathway plays a pathogenetic role in tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). Lymphoid enhancer binding factor 1 (LEF1), a key mediator of Wnt signaling, has been linked to leukemic transformation, and LEF1 mutations have been identified in T-ALL. Here we found LEF1 is highly expressed in 25.0% adult ALL patients and LEF1 high expression was associated with high-risk leukemia factors (high WBC, Philadelphia chromosome positive, complex karyotype), shorter event-free survival (EFS), and high relapse rates in patients with B-ALL. LEF1 high expression is also associated with high mutation rate of Notch1 and JAK1 in T-ALL. We identified 2 novel LEF1 mutations (K86E and P106L) in 4 of 131 patients with ALL, and those patients with high-risk ALL (high WBC, complex karyotype). These results suggest a role for LEF1 mutations in leukemogenesis. We further explored the effect of the mutations on cell proliferation and found both mutations significantly promoted the proliferation of ALL cells. We also observed the effect of LEF1 and its mutations on the transcription of its targets, c-MYC and Cyclin D1. We found LEF1 increased the promoter activity of its targets c-MYC and Cyclin D1, and LEF1 K86E and P106L mutants further significantly enhanced this effect. We also observed that the c-MYC and Cyclin D1 mRNA levels were significantly increased in patients with LEF1 high expression compared with those with low expression. Taken together, our findings indicate high LEF1 expression and mutation are associated with high-risk leukemia and our results also revealed that LEF1 high expression and/or gain-of-function mutations are involved in leukemogenesis of ALL.

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“…Previous study suggests a possible link between the degree of LEF1 overexpression and poor prognosis in adult B‐precursor ALL and chronic lymphocytic leukemia . However, a more recent study showed that high LEF1 level is a favorable prognostic factor in cytogenetically normal acute myeloid leukemia (CN‐AML) , AML , and acute promyelocytic leukemia (APL) of adult patients. Here, our study reports that high LEF1 expression is associated with favorable CR rate and OS in childhood ALL.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of lymphoid enhancer‐binding factor‐1 (LEF1) is a novel favorable prognostic factor in childhood acute lymphoblastic leukemia

Jia

et al. 2015

Int J Lab Hematology

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Lymphoid enhancer binding factor-1 (LEF1) expression as a prognostic factor in adult acute promyelocytic leukemia

Cited by 20 publications

References 49 publications

Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients

Prognostic Impact of Lymphoid Enhancer Factor 1 Expression and Serum Galectin.3 in Egyptian AML Patients

Characterization of LEF1 High Expression and Novel Mutations in Adult Acute Lymphoblastic Leukemia

Overexpression of lymphoid enhancer‐binding factor‐1 (LEF1) is a novel favorable prognostic factor in childhood acute lymphoblastic leukemia

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