Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia
Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL. Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leuk...
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Format: | Article |
Language: | Russian |
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Practical Medicine Publishing House
2016-01-01
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Series: | Kliničeskaâ onkogematologiâ |
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Online Access: | http://bloodjournal.ru/en/relation-between-genomic-dna-breakpoints-in-mll-gene-and-treatment-outcome-in-infants-with-acute-leukemia/ |
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Article |
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DOAJ |
language |
Russian |
format |
Article |
sources |
DOAJ |
author |
GA Tsaur C Meyer TO Riger AM Kustanovich EV Fleischman YuV Ol’shanskaya AM Popov OI Sokova EA Matveeva OV Nikulina AE Drui OR Arakaev OV Streneva SA Rumyantsev EV Shorikov AG Solodovnikov LI Savel’ev R Marschalek LG Fechina |
spellingShingle |
GA Tsaur C Meyer TO Riger AM Kustanovich EV Fleischman YuV Ol’shanskaya AM Popov OI Sokova EA Matveeva OV Nikulina AE Drui OR Arakaev OV Streneva SA Rumyantsev EV Shorikov AG Solodovnikov LI Savel’ev R Marschalek LG Fechina Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia Kliničeskaâ onkogematologiâ acute leukemia infants 11q23/MLL rearrangements MLL-Baby treatment outcome |
author_facet |
GA Tsaur C Meyer TO Riger AM Kustanovich EV Fleischman YuV Ol’shanskaya AM Popov OI Sokova EA Matveeva OV Nikulina AE Drui OR Arakaev OV Streneva SA Rumyantsev EV Shorikov AG Solodovnikov LI Savel’ev R Marschalek LG Fechina |
author_sort |
GA Tsaur |
title |
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia |
title_short |
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia |
title_full |
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia |
title_fullStr |
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia |
title_full_unstemmed |
Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia |
title_sort |
relation between genomic dna breakpoints in mll gene and treatment outcome in infants with acute leukemia |
publisher |
Practical Medicine Publishing House |
series |
Kliničeskaâ onkogematologiâ |
issn |
1997-6933 2500-2139 |
publishDate |
2016-01-01 |
description |
Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL.
Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study.
Results. 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, p < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome.
Conclusion. Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL. |
topic |
acute leukemia infants 11q23/MLL rearrangements MLL-Baby treatment outcome |
url |
http://bloodjournal.ru/en/relation-between-genomic-dna-breakpoints-in-mll-gene-and-treatment-outcome-in-infants-with-acute-leukemia/ |
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doaj-0db49f9820234c13a26b0aa3e916b17d2020-11-24T23:33:12ZrusPractical Medicine Publishing HouseKliničeskaâ onkogematologiâ1997-69332500-21392016-01-0191222910.21320/2500-2139-2016-9-1-22-29Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute LeukemiaGA Tsaur0C Meyer1TO Riger2 AM Kustanovich3EV Fleischman4YuV Ol’shanskaya5AM Popov6OI Sokova7EA Matveeva8OV Nikulina9AE Drui10OR Arakaev11OV Streneva12SA Rumyantsev13EV Shorikov14AG Solodovnikov15LI Savel’ev16R Marschalek17LG Fechina18Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026; First President of Russia B.N. Yeltsin Ural Federal University , 19 Mira str., Ekaterinburg, Russian Federation, 620002Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, N230, Max-von-Laue Str. 9, Frankfurt am Main Deutschland, 60438Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, 43 Frunzenskaya str., Borovlyany, Minsk District, Belarus, 223053N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, N230, Max-von-Laue Str. 9, Frankfurt am Main Deutschland, 60438Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL. Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study. Results. 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, p < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome. Conclusion. Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL.http://bloodjournal.ru/en/relation-between-genomic-dna-breakpoints-in-mll-gene-and-treatment-outcome-in-infants-with-acute-leukemia/acute leukemiainfants11q23/MLL rearrangementsMLL-Babytreatment outcome |