SLOWER EARLY RESPONSE TO TREATMENT AND DISTINCT EXPRESSION PROFILE OF CHILDHOOD HIGH HYPERDIPLOID ACUTE LYMPHOBLASTIC LEUKAEMIA WITH DNA INDEX <1.16
(Abstract release date: 05/19/16)
EHA Library. Zuna J. 06/09/16; 132395; E846
Dr. Jan Zuna
Contributions
Contributions
Abstract
Abstract: E846
Type: Eposter Presentation
Background
Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes in leukaemic cells are defined as high-hyperdiploid (HHD). Besides the number of chromosomes, the hyperdiploid ALL can be determined also by DNA index (DNAi; established by flow cytometry), representing ratio of DNA content in leukaemic vs. normal diploid cells. In childhood, HHD leukaemias comprise 25-30% of all cases, typically arise from B lymphocyte precursors and are generally associated with good prognosis. However, several studies show heterogeneity in HHD-ALL and suggest that the favourable prognosis is associated rather with cases presenting with higher ploidy defined by DNAi >=1.16 or with a presence of specific single or combined trisomies. Thus, cases with DNA index >=1.16 and <1.6 are often considered as “typical” high hyperdiploid ALLs while leukemias with >50 chromosomes and DNA index <1.16 are only rarely studied separately.
Aims
In this study we analysed childhood HHD-ALL patients divided into groups with lower (<1.16) and higher (>=1.16) DNAi to reveal biological and clinical differences between the two subgroups.
Methods
Eighty-nine childhood HHD-ALL patients were analysed by single nucleotide polymorphism array to determine extra chromosomes and to correlate the data with DNA content established by flow cytometry. Moreover, we analysed treatment response, presence of secondary aberrations, mutations in Ras pathway genes (NRAS, KRAS, FLT3, PTPN11) and also gene expression profile (GEP) to reveal possible differences between the two subgroups.
Results
Our results show that vast majority of cases with 51 to 54 chromosomes have DNAi between 1.1 and 1.16 and cases with 55 and more chromosomes have usually DNAi >=1.16. The groups with lower and higher DNAi have distinct response to early treatment - the better response of the group with higher DNAi is probably associated with specific chromosomal gains (trisomy of chromosome 10 or combined with trisomies 4 and/or 17) highly enriched in the group with higher DNAi. Moreover, patients with lower and higher DNAi show distinct GEP in unsupervised clustering analysis; importantly, analysis of the differentially expressed genes and number of its genomic copies suggests, that gene dosage effect probably does not play a driving role in the different behaviour of the two HHD-ALL subgroups.
Conclusion
The distinct GEP suggests that cytogenetically defined HHD-ALL is in fact composed of two biologically distinguishable subgroups. These differences should be taken into account when defining ALL with excellent prognosis; if treatment deintensification is considered for childhood HHD ALL, only cases with DNAi >=1.16 and gain of chromosome 10 plus chromosomes 4 and/or 17 should be taken into account.Support: The study was supported by grants from Ministry of Health, Czech Republic: IGA NT/14350-3 and project 00064203 (UH Motol).
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Gene expression profile, Hyperdiploid, Single nucleotide polymorphism
Type: Eposter Presentation
Background
Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes in leukaemic cells are defined as high-hyperdiploid (HHD). Besides the number of chromosomes, the hyperdiploid ALL can be determined also by DNA index (DNAi; established by flow cytometry), representing ratio of DNA content in leukaemic vs. normal diploid cells. In childhood, HHD leukaemias comprise 25-30% of all cases, typically arise from B lymphocyte precursors and are generally associated with good prognosis. However, several studies show heterogeneity in HHD-ALL and suggest that the favourable prognosis is associated rather with cases presenting with higher ploidy defined by DNAi >=1.16 or with a presence of specific single or combined trisomies. Thus, cases with DNA index >=1.16 and <1.6 are often considered as “typical” high hyperdiploid ALLs while leukemias with >50 chromosomes and DNA index <1.16 are only rarely studied separately.
Aims
In this study we analysed childhood HHD-ALL patients divided into groups with lower (<1.16) and higher (>=1.16) DNAi to reveal biological and clinical differences between the two subgroups.
Methods
Eighty-nine childhood HHD-ALL patients were analysed by single nucleotide polymorphism array to determine extra chromosomes and to correlate the data with DNA content established by flow cytometry. Moreover, we analysed treatment response, presence of secondary aberrations, mutations in Ras pathway genes (NRAS, KRAS, FLT3, PTPN11) and also gene expression profile (GEP) to reveal possible differences between the two subgroups.
Results
Our results show that vast majority of cases with 51 to 54 chromosomes have DNAi between 1.1 and 1.16 and cases with 55 and more chromosomes have usually DNAi >=1.16. The groups with lower and higher DNAi have distinct response to early treatment - the better response of the group with higher DNAi is probably associated with specific chromosomal gains (trisomy of chromosome 10 or combined with trisomies 4 and/or 17) highly enriched in the group with higher DNAi. Moreover, patients with lower and higher DNAi show distinct GEP in unsupervised clustering analysis; importantly, analysis of the differentially expressed genes and number of its genomic copies suggests, that gene dosage effect probably does not play a driving role in the different behaviour of the two HHD-ALL subgroups.
Conclusion
The distinct GEP suggests that cytogenetically defined HHD-ALL is in fact composed of two biologically distinguishable subgroups. These differences should be taken into account when defining ALL with excellent prognosis; if treatment deintensification is considered for childhood HHD ALL, only cases with DNAi >=1.16 and gain of chromosome 10 plus chromosomes 4 and/or 17 should be taken into account.Support: The study was supported by grants from Ministry of Health, Czech Republic: IGA NT/14350-3 and project 00064203 (UH Motol).
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Gene expression profile, Hyperdiploid, Single nucleotide polymorphism
Abstract: E846
Type: Eposter Presentation
Background
Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes in leukaemic cells are defined as high-hyperdiploid (HHD). Besides the number of chromosomes, the hyperdiploid ALL can be determined also by DNA index (DNAi; established by flow cytometry), representing ratio of DNA content in leukaemic vs. normal diploid cells. In childhood, HHD leukaemias comprise 25-30% of all cases, typically arise from B lymphocyte precursors and are generally associated with good prognosis. However, several studies show heterogeneity in HHD-ALL and suggest that the favourable prognosis is associated rather with cases presenting with higher ploidy defined by DNAi >=1.16 or with a presence of specific single or combined trisomies. Thus, cases with DNA index >=1.16 and <1.6 are often considered as “typical” high hyperdiploid ALLs while leukemias with >50 chromosomes and DNA index <1.16 are only rarely studied separately.
Aims
In this study we analysed childhood HHD-ALL patients divided into groups with lower (<1.16) and higher (>=1.16) DNAi to reveal biological and clinical differences between the two subgroups.
Methods
Eighty-nine childhood HHD-ALL patients were analysed by single nucleotide polymorphism array to determine extra chromosomes and to correlate the data with DNA content established by flow cytometry. Moreover, we analysed treatment response, presence of secondary aberrations, mutations in Ras pathway genes (NRAS, KRAS, FLT3, PTPN11) and also gene expression profile (GEP) to reveal possible differences between the two subgroups.
Results
Our results show that vast majority of cases with 51 to 54 chromosomes have DNAi between 1.1 and 1.16 and cases with 55 and more chromosomes have usually DNAi >=1.16. The groups with lower and higher DNAi have distinct response to early treatment - the better response of the group with higher DNAi is probably associated with specific chromosomal gains (trisomy of chromosome 10 or combined with trisomies 4 and/or 17) highly enriched in the group with higher DNAi. Moreover, patients with lower and higher DNAi show distinct GEP in unsupervised clustering analysis; importantly, analysis of the differentially expressed genes and number of its genomic copies suggests, that gene dosage effect probably does not play a driving role in the different behaviour of the two HHD-ALL subgroups.
Conclusion
The distinct GEP suggests that cytogenetically defined HHD-ALL is in fact composed of two biologically distinguishable subgroups. These differences should be taken into account when defining ALL with excellent prognosis; if treatment deintensification is considered for childhood HHD ALL, only cases with DNAi >=1.16 and gain of chromosome 10 plus chromosomes 4 and/or 17 should be taken into account.Support: The study was supported by grants from Ministry of Health, Czech Republic: IGA NT/14350-3 and project 00064203 (UH Motol).
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Gene expression profile, Hyperdiploid, Single nucleotide polymorphism
Type: Eposter Presentation
Background
Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes in leukaemic cells are defined as high-hyperdiploid (HHD). Besides the number of chromosomes, the hyperdiploid ALL can be determined also by DNA index (DNAi; established by flow cytometry), representing ratio of DNA content in leukaemic vs. normal diploid cells. In childhood, HHD leukaemias comprise 25-30% of all cases, typically arise from B lymphocyte precursors and are generally associated with good prognosis. However, several studies show heterogeneity in HHD-ALL and suggest that the favourable prognosis is associated rather with cases presenting with higher ploidy defined by DNAi >=1.16 or with a presence of specific single or combined trisomies. Thus, cases with DNA index >=1.16 and <1.6 are often considered as “typical” high hyperdiploid ALLs while leukemias with >50 chromosomes and DNA index <1.16 are only rarely studied separately.
Aims
In this study we analysed childhood HHD-ALL patients divided into groups with lower (<1.16) and higher (>=1.16) DNAi to reveal biological and clinical differences between the two subgroups.
Methods
Eighty-nine childhood HHD-ALL patients were analysed by single nucleotide polymorphism array to determine extra chromosomes and to correlate the data with DNA content established by flow cytometry. Moreover, we analysed treatment response, presence of secondary aberrations, mutations in Ras pathway genes (NRAS, KRAS, FLT3, PTPN11) and also gene expression profile (GEP) to reveal possible differences between the two subgroups.
Results
Our results show that vast majority of cases with 51 to 54 chromosomes have DNAi between 1.1 and 1.16 and cases with 55 and more chromosomes have usually DNAi >=1.16. The groups with lower and higher DNAi have distinct response to early treatment - the better response of the group with higher DNAi is probably associated with specific chromosomal gains (trisomy of chromosome 10 or combined with trisomies 4 and/or 17) highly enriched in the group with higher DNAi. Moreover, patients with lower and higher DNAi show distinct GEP in unsupervised clustering analysis; importantly, analysis of the differentially expressed genes and number of its genomic copies suggests, that gene dosage effect probably does not play a driving role in the different behaviour of the two HHD-ALL subgroups.
Conclusion
The distinct GEP suggests that cytogenetically defined HHD-ALL is in fact composed of two biologically distinguishable subgroups. These differences should be taken into account when defining ALL with excellent prognosis; if treatment deintensification is considered for childhood HHD ALL, only cases with DNAi >=1.16 and gain of chromosome 10 plus chromosomes 4 and/or 17 should be taken into account.Support: The study was supported by grants from Ministry of Health, Czech Republic: IGA NT/14350-3 and project 00064203 (UH Motol).
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Gene expression profile, Hyperdiploid, Single nucleotide polymorphism
{{ help_message }}
{{filter}}