LOW EXPRESSION OF LYMPHOID ENHANCER-BINDING FACTOR-1 (LEF1) ASSOCIATES WITH POOR PROGNOSTIC FACTORS IN PEDIATRIC ACUTE LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Camós M. 06/09/16; 132417; E868
Mireia Camós
Contributions
Contributions
Abstract
Abstract: E868
Type: Eposter Presentation
Background
LEF1 expression has been described in different types of leukemia, but its prognostic impact remains controversial. In adult patients with acute lymphoblastic leukemia (ALL), LEF1 overexpression correlates to high-risk factors (hyperleukocytosis, BCR-ABL1 rearrangement and complex karyotype). In contrast, overexpression of LEF1 is a favorable prognostic factor in childhood ALL and in acute myeloblastic leukemia (AML), both in adults and children.
Aims
to analyze the prognostic impact of LEF1 expression in a series of pediatric patients diagnosed with acute leukemia in a single center.
Methods
we included pediatric patients (0-18 years) with de novo acute leukemia, treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society from 2003 to 2015. mRNA expression levels of LEF1 were assayed by quantitative PCR and analyzed with the 2-DDCt method, with non-neoplastic samples used as controls for the relative quantification. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression level: LEF1high (Q4) and LEF1low (Q1-Q3). Correlations with clinical and biological variables and survival analysis were performed with non-parametric, chi-square and Kaplan-Meier tests and log-rank comparison for subgroups.
Results
we analyzed 104 patients, with a median age of 4.7 years (0-17.4), including 61 boys (59%). Sixty-two patients (60%) had B-cell precursor ALL (all main cytogenetic subtypes represented), 22 patients (21%) had T-cell ALL and 20 cases AML (19%). Our AML series was enriched in infants: the median age was 2.7 (0.08-15.96), included 5 infants (25%) and 8 MLL rearranged cases (40%). Median expression level of LEF1 was 6.44 (0-461), and differed significantly according to lineage (21.6 (0.1-461) in B-ALL; 4.7 (0.01-79.3) in T-ALL and 0.18 (0-13.5) in AML, p<0.0001). In the whole series of patients, LEF1low expression was observed predominantly in infants and in patients with MLL rearrangement (p=0.043 and p=0.011, respectively). In addition, a trend to hyperleukocytosis was observed in patients with LEF1low (p=0.06). After a median follow-up of 4.3 years (0.06-14.96), 14 patients died and 13 relapsed. The overall survival (OS) at 5 years was 94±3% in B-ALL patients, 80±9% in T-ALL and 63±11% in AML patients, p=0.001. In B-ALL subgroup of patients, low expression of LEF1 was again significantly correlated to infant cases (p=0.025). Interestingly, in T-ALL patients we observed different findings: those cases with high expression of LEF1 associated with older age (p=0.025) and worse event free survival (EFS, 61±15% vs 100%, p=0.02), although the number of patients is low and our results must be taken with caution. Despite the number of patients precluded the finding of statistical significance, in AML cases we observed, as in the whole series of patients, a correlation between LEF1low and age <1 year, MLL rearrangement and higher WBC count (p=0.08, p=0.055 and p=0.072, respectively).
Conclusion
in our series of pediatric patients, low LEF1 expression levels in B-ALL and AML patients correlated to adverse prognostic factors, such as age <1 year, MLL rearrangement and hyperleukocytosis. A larger number of patients is needed to confirm our results.GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute leukemia, Gene expression, Pediatric, Prognostic factor
Type: Eposter Presentation
Background
LEF1 expression has been described in different types of leukemia, but its prognostic impact remains controversial. In adult patients with acute lymphoblastic leukemia (ALL), LEF1 overexpression correlates to high-risk factors (hyperleukocytosis, BCR-ABL1 rearrangement and complex karyotype). In contrast, overexpression of LEF1 is a favorable prognostic factor in childhood ALL and in acute myeloblastic leukemia (AML), both in adults and children.
Aims
to analyze the prognostic impact of LEF1 expression in a series of pediatric patients diagnosed with acute leukemia in a single center.
Methods
we included pediatric patients (0-18 years) with de novo acute leukemia, treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society from 2003 to 2015. mRNA expression levels of LEF1 were assayed by quantitative PCR and analyzed with the 2-DDCt method, with non-neoplastic samples used as controls for the relative quantification. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression level: LEF1high (Q4) and LEF1low (Q1-Q3). Correlations with clinical and biological variables and survival analysis were performed with non-parametric, chi-square and Kaplan-Meier tests and log-rank comparison for subgroups.
Results
we analyzed 104 patients, with a median age of 4.7 years (0-17.4), including 61 boys (59%). Sixty-two patients (60%) had B-cell precursor ALL (all main cytogenetic subtypes represented), 22 patients (21%) had T-cell ALL and 20 cases AML (19%). Our AML series was enriched in infants: the median age was 2.7 (0.08-15.96), included 5 infants (25%) and 8 MLL rearranged cases (40%). Median expression level of LEF1 was 6.44 (0-461), and differed significantly according to lineage (21.6 (0.1-461) in B-ALL; 4.7 (0.01-79.3) in T-ALL and 0.18 (0-13.5) in AML, p<0.0001). In the whole series of patients, LEF1low expression was observed predominantly in infants and in patients with MLL rearrangement (p=0.043 and p=0.011, respectively). In addition, a trend to hyperleukocytosis was observed in patients with LEF1low (p=0.06). After a median follow-up of 4.3 years (0.06-14.96), 14 patients died and 13 relapsed. The overall survival (OS) at 5 years was 94±3% in B-ALL patients, 80±9% in T-ALL and 63±11% in AML patients, p=0.001. In B-ALL subgroup of patients, low expression of LEF1 was again significantly correlated to infant cases (p=0.025). Interestingly, in T-ALL patients we observed different findings: those cases with high expression of LEF1 associated with older age (p=0.025) and worse event free survival (EFS, 61±15% vs 100%, p=0.02), although the number of patients is low and our results must be taken with caution. Despite the number of patients precluded the finding of statistical significance, in AML cases we observed, as in the whole series of patients, a correlation between LEF1low and age <1 year, MLL rearrangement and higher WBC count (p=0.08, p=0.055 and p=0.072, respectively).
Conclusion
in our series of pediatric patients, low LEF1 expression levels in B-ALL and AML patients correlated to adverse prognostic factors, such as age <1 year, MLL rearrangement and hyperleukocytosis. A larger number of patients is needed to confirm our results.GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute leukemia, Gene expression, Pediatric, Prognostic factor
Abstract: E868
Type: Eposter Presentation
Background
LEF1 expression has been described in different types of leukemia, but its prognostic impact remains controversial. In adult patients with acute lymphoblastic leukemia (ALL), LEF1 overexpression correlates to high-risk factors (hyperleukocytosis, BCR-ABL1 rearrangement and complex karyotype). In contrast, overexpression of LEF1 is a favorable prognostic factor in childhood ALL and in acute myeloblastic leukemia (AML), both in adults and children.
Aims
to analyze the prognostic impact of LEF1 expression in a series of pediatric patients diagnosed with acute leukemia in a single center.
Methods
we included pediatric patients (0-18 years) with de novo acute leukemia, treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society from 2003 to 2015. mRNA expression levels of LEF1 were assayed by quantitative PCR and analyzed with the 2-DDCt method, with non-neoplastic samples used as controls for the relative quantification. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression level: LEF1high (Q4) and LEF1low (Q1-Q3). Correlations with clinical and biological variables and survival analysis were performed with non-parametric, chi-square and Kaplan-Meier tests and log-rank comparison for subgroups.
Results
we analyzed 104 patients, with a median age of 4.7 years (0-17.4), including 61 boys (59%). Sixty-two patients (60%) had B-cell precursor ALL (all main cytogenetic subtypes represented), 22 patients (21%) had T-cell ALL and 20 cases AML (19%). Our AML series was enriched in infants: the median age was 2.7 (0.08-15.96), included 5 infants (25%) and 8 MLL rearranged cases (40%). Median expression level of LEF1 was 6.44 (0-461), and differed significantly according to lineage (21.6 (0.1-461) in B-ALL; 4.7 (0.01-79.3) in T-ALL and 0.18 (0-13.5) in AML, p<0.0001). In the whole series of patients, LEF1low expression was observed predominantly in infants and in patients with MLL rearrangement (p=0.043 and p=0.011, respectively). In addition, a trend to hyperleukocytosis was observed in patients with LEF1low (p=0.06). After a median follow-up of 4.3 years (0.06-14.96), 14 patients died and 13 relapsed. The overall survival (OS) at 5 years was 94±3% in B-ALL patients, 80±9% in T-ALL and 63±11% in AML patients, p=0.001. In B-ALL subgroup of patients, low expression of LEF1 was again significantly correlated to infant cases (p=0.025). Interestingly, in T-ALL patients we observed different findings: those cases with high expression of LEF1 associated with older age (p=0.025) and worse event free survival (EFS, 61±15% vs 100%, p=0.02), although the number of patients is low and our results must be taken with caution. Despite the number of patients precluded the finding of statistical significance, in AML cases we observed, as in the whole series of patients, a correlation between LEF1low and age <1 year, MLL rearrangement and higher WBC count (p=0.08, p=0.055 and p=0.072, respectively).
Conclusion
in our series of pediatric patients, low LEF1 expression levels in B-ALL and AML patients correlated to adverse prognostic factors, such as age <1 year, MLL rearrangement and hyperleukocytosis. A larger number of patients is needed to confirm our results.GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute leukemia, Gene expression, Pediatric, Prognostic factor
Type: Eposter Presentation
Background
LEF1 expression has been described in different types of leukemia, but its prognostic impact remains controversial. In adult patients with acute lymphoblastic leukemia (ALL), LEF1 overexpression correlates to high-risk factors (hyperleukocytosis, BCR-ABL1 rearrangement and complex karyotype). In contrast, overexpression of LEF1 is a favorable prognostic factor in childhood ALL and in acute myeloblastic leukemia (AML), both in adults and children.
Aims
to analyze the prognostic impact of LEF1 expression in a series of pediatric patients diagnosed with acute leukemia in a single center.
Methods
we included pediatric patients (0-18 years) with de novo acute leukemia, treated according to consecutive protocols of the Spanish Hematology and Oncology Pediatric Society from 2003 to 2015. mRNA expression levels of LEF1 were assayed by quantitative PCR and analyzed with the 2-DDCt method, with non-neoplastic samples used as controls for the relative quantification. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression level: LEF1high (Q4) and LEF1low (Q1-Q3). Correlations with clinical and biological variables and survival analysis were performed with non-parametric, chi-square and Kaplan-Meier tests and log-rank comparison for subgroups.
Results
we analyzed 104 patients, with a median age of 4.7 years (0-17.4), including 61 boys (59%). Sixty-two patients (60%) had B-cell precursor ALL (all main cytogenetic subtypes represented), 22 patients (21%) had T-cell ALL and 20 cases AML (19%). Our AML series was enriched in infants: the median age was 2.7 (0.08-15.96), included 5 infants (25%) and 8 MLL rearranged cases (40%). Median expression level of LEF1 was 6.44 (0-461), and differed significantly according to lineage (21.6 (0.1-461) in B-ALL; 4.7 (0.01-79.3) in T-ALL and 0.18 (0-13.5) in AML, p<0.0001). In the whole series of patients, LEF1low expression was observed predominantly in infants and in patients with MLL rearrangement (p=0.043 and p=0.011, respectively). In addition, a trend to hyperleukocytosis was observed in patients with LEF1low (p=0.06). After a median follow-up of 4.3 years (0.06-14.96), 14 patients died and 13 relapsed. The overall survival (OS) at 5 years was 94±3% in B-ALL patients, 80±9% in T-ALL and 63±11% in AML patients, p=0.001. In B-ALL subgroup of patients, low expression of LEF1 was again significantly correlated to infant cases (p=0.025). Interestingly, in T-ALL patients we observed different findings: those cases with high expression of LEF1 associated with older age (p=0.025) and worse event free survival (EFS, 61±15% vs 100%, p=0.02), although the number of patients is low and our results must be taken with caution. Despite the number of patients precluded the finding of statistical significance, in AML cases we observed, as in the whole series of patients, a correlation between LEF1low and age <1 year, MLL rearrangement and higher WBC count (p=0.08, p=0.055 and p=0.072, respectively).
Conclusion
in our series of pediatric patients, low LEF1 expression levels in B-ALL and AML patients correlated to adverse prognostic factors, such as age <1 year, MLL rearrangement and hyperleukocytosis. A larger number of patients is needed to confirm our results.GRANTS: PI12/2417, PN I+D+I, ISCIII (SGE, FIS), CIBERER, Fundación AECC, Fundación Sandra Ibarra, Fundación Cris contra el cáncer & “Força Miquel”, “Candela” & “Mua” projects.
Session topic: E-poster
Keyword(s): Acute leukemia, Gene expression, Pediatric, Prognostic factor
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