EARLY IDENTIFICATION OF CALM-AF10 MUTATION BY MOLECULAR PROFILING HELPS TO RISK STRATIFY HIGH RISK T-ALL FOR EARLY VUD ALLOGENEIC BONE MARROW TRANSPLANT.
(Abstract release date: 05/19/16)
EHA Library. Prahladan M. 06/09/16; 134517; PB1617
Mahesh Prahladan
Contributions
Contributions
Abstract
Abstract: PB1617
Type: Publication Only
Background
The t(10;11)(p12;q23) and t(10;11)(p12;q14) translocations, which encodethe clathrin-assembly protein-like lymphoid myeloid leukemia gene(PICALM)- MLLT10 (formerly CALM-AF10), are recurrent chromosomalrearrangements found in some patients with T-cell acute lymphoblasticleukemia (T-ALL), and are associated with poor outcomes to standardchemotherapy. PICALM-MLLT10-positive cases often have positiveexpression of CD13, CD33 or CD34, but negative expression of theT-lineage markers CD5, TdT, cCD3 and CD7.
Aims
Mutational analysis on RT-PCR in conjunction with flowcytometry, fluorescent in situ hybridization (FISH) and metaphasekaryotyping, increases the sensitivity for detecting primary andsecondary cytogenetic abnormalities in patients with high-risk T-ALL.
Methods
We report a 34-year-old lady with T-ALL who presented with amediastinal mass. Blast cells in the bone marrow aspirate demonstratedstrong expression of CD7, CD13, CD56, HLA-DR, cytoplasmic CD3, andequivocal expression of CD99. No other T-cell-associated antigens weredetectable (including CD1a, CD2, surface CD3, CD4, CD5, CD8, CD16, CD57,CD34 and TdT). The T-Lymphoblastic Leukaemia FISH panel was negative.Chromosomal analysis showed 46,XX,t(10;11)(p13;q14)[5]/46,XX, withbalanced reciprocal translocation between the short arm of chromosome 10and the long arm of chromosome 11. Genome molecular profiling showedrecurrent translocation PICALM-MLLT10 [CALM-AF10];t(10;11)(p13;q14) withno disruption of the MLL (11q23) locus, confirming the negative MLL FISHresult. The patient achieved complete remission following phase-twoinduction on the UKALL14 protocol and elected to have a volunteerunrelated donor (VUD) myeloablative allogeneic bone marrow transplant.She remains in complete remission 14 months post-transplant.
Results
The positive outcome for our patient, following allogeneic transplant,reflects similar reports from the UKALLXII/ECOG2993 trial for patientswith the MLLT10 [CALM-AF10];t(10;11)(p13;q14) mutation. The use ofmutational analysis on RT-PCR early in the diagnostic process, in thiscase, allowed prompt detection of a high-risk cytogenetic abnormalityand more accurate risk stratification that guided the decision toproceed to allogeneic transplant.
Conclusion
Early identification of high risk cytogenetic abnormality incorporating mutational analysis using RT -PCR along with immunophenotype, FISH and karyotype help to risk stratify patients for allogeneic bone marrow transplant resulting in successful outcome in patients with in high risk T-ALL.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, CALM/AF10, T-ALL
Type: Publication Only
Background
The t(10;11)(p12;q23) and t(10;11)(p12;q14) translocations, which encodethe clathrin-assembly protein-like lymphoid myeloid leukemia gene(PICALM)- MLLT10 (formerly CALM-AF10), are recurrent chromosomalrearrangements found in some patients with T-cell acute lymphoblasticleukemia (T-ALL), and are associated with poor outcomes to standardchemotherapy. PICALM-MLLT10-positive cases often have positiveexpression of CD13, CD33 or CD34, but negative expression of theT-lineage markers CD5, TdT, cCD3 and CD7.
Aims
Mutational analysis on RT-PCR in conjunction with flowcytometry, fluorescent in situ hybridization (FISH) and metaphasekaryotyping, increases the sensitivity for detecting primary andsecondary cytogenetic abnormalities in patients with high-risk T-ALL.
Methods
We report a 34-year-old lady with T-ALL who presented with amediastinal mass. Blast cells in the bone marrow aspirate demonstratedstrong expression of CD7, CD13, CD56, HLA-DR, cytoplasmic CD3, andequivocal expression of CD99. No other T-cell-associated antigens weredetectable (including CD1a, CD2, surface CD3, CD4, CD5, CD8, CD16, CD57,CD34 and TdT). The T-Lymphoblastic Leukaemia FISH panel was negative.Chromosomal analysis showed 46,XX,t(10;11)(p13;q14)[5]/46,XX, withbalanced reciprocal translocation between the short arm of chromosome 10and the long arm of chromosome 11. Genome molecular profiling showedrecurrent translocation PICALM-MLLT10 [CALM-AF10];t(10;11)(p13;q14) withno disruption of the MLL (11q23) locus, confirming the negative MLL FISHresult. The patient achieved complete remission following phase-twoinduction on the UKALL14 protocol and elected to have a volunteerunrelated donor (VUD) myeloablative allogeneic bone marrow transplant.She remains in complete remission 14 months post-transplant.
Results
The positive outcome for our patient, following allogeneic transplant,reflects similar reports from the UKALLXII/ECOG2993 trial for patientswith the MLLT10 [CALM-AF10];t(10;11)(p13;q14) mutation. The use ofmutational analysis on RT-PCR early in the diagnostic process, in thiscase, allowed prompt detection of a high-risk cytogenetic abnormalityand more accurate risk stratification that guided the decision toproceed to allogeneic transplant.
Conclusion
Early identification of high risk cytogenetic abnormality incorporating mutational analysis using RT -PCR along with immunophenotype, FISH and karyotype help to risk stratify patients for allogeneic bone marrow transplant resulting in successful outcome in patients with in high risk T-ALL.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, CALM/AF10, T-ALL
Abstract: PB1617
Type: Publication Only
Background
The t(10;11)(p12;q23) and t(10;11)(p12;q14) translocations, which encodethe clathrin-assembly protein-like lymphoid myeloid leukemia gene(PICALM)- MLLT10 (formerly CALM-AF10), are recurrent chromosomalrearrangements found in some patients with T-cell acute lymphoblasticleukemia (T-ALL), and are associated with poor outcomes to standardchemotherapy. PICALM-MLLT10-positive cases often have positiveexpression of CD13, CD33 or CD34, but negative expression of theT-lineage markers CD5, TdT, cCD3 and CD7.
Aims
Mutational analysis on RT-PCR in conjunction with flowcytometry, fluorescent in situ hybridization (FISH) and metaphasekaryotyping, increases the sensitivity for detecting primary andsecondary cytogenetic abnormalities in patients with high-risk T-ALL.
Methods
We report a 34-year-old lady with T-ALL who presented with amediastinal mass. Blast cells in the bone marrow aspirate demonstratedstrong expression of CD7, CD13, CD56, HLA-DR, cytoplasmic CD3, andequivocal expression of CD99. No other T-cell-associated antigens weredetectable (including CD1a, CD2, surface CD3, CD4, CD5, CD8, CD16, CD57,CD34 and TdT). The T-Lymphoblastic Leukaemia FISH panel was negative.Chromosomal analysis showed 46,XX,t(10;11)(p13;q14)[5]/46,XX, withbalanced reciprocal translocation between the short arm of chromosome 10and the long arm of chromosome 11. Genome molecular profiling showedrecurrent translocation PICALM-MLLT10 [CALM-AF10];t(10;11)(p13;q14) withno disruption of the MLL (11q23) locus, confirming the negative MLL FISHresult. The patient achieved complete remission following phase-twoinduction on the UKALL14 protocol and elected to have a volunteerunrelated donor (VUD) myeloablative allogeneic bone marrow transplant.She remains in complete remission 14 months post-transplant.
Results
The positive outcome for our patient, following allogeneic transplant,reflects similar reports from the UKALLXII/ECOG2993 trial for patientswith the MLLT10 [CALM-AF10];t(10;11)(p13;q14) mutation. The use ofmutational analysis on RT-PCR early in the diagnostic process, in thiscase, allowed prompt detection of a high-risk cytogenetic abnormalityand more accurate risk stratification that guided the decision toproceed to allogeneic transplant.
Conclusion
Early identification of high risk cytogenetic abnormality incorporating mutational analysis using RT -PCR along with immunophenotype, FISH and karyotype help to risk stratify patients for allogeneic bone marrow transplant resulting in successful outcome in patients with in high risk T-ALL.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, CALM/AF10, T-ALL
Type: Publication Only
Background
The t(10;11)(p12;q23) and t(10;11)(p12;q14) translocations, which encodethe clathrin-assembly protein-like lymphoid myeloid leukemia gene(PICALM)- MLLT10 (formerly CALM-AF10), are recurrent chromosomalrearrangements found in some patients with T-cell acute lymphoblasticleukemia (T-ALL), and are associated with poor outcomes to standardchemotherapy. PICALM-MLLT10-positive cases often have positiveexpression of CD13, CD33 or CD34, but negative expression of theT-lineage markers CD5, TdT, cCD3 and CD7.
Aims
Mutational analysis on RT-PCR in conjunction with flowcytometry, fluorescent in situ hybridization (FISH) and metaphasekaryotyping, increases the sensitivity for detecting primary andsecondary cytogenetic abnormalities in patients with high-risk T-ALL.
Methods
We report a 34-year-old lady with T-ALL who presented with amediastinal mass. Blast cells in the bone marrow aspirate demonstratedstrong expression of CD7, CD13, CD56, HLA-DR, cytoplasmic CD3, andequivocal expression of CD99. No other T-cell-associated antigens weredetectable (including CD1a, CD2, surface CD3, CD4, CD5, CD8, CD16, CD57,CD34 and TdT). The T-Lymphoblastic Leukaemia FISH panel was negative.Chromosomal analysis showed 46,XX,t(10;11)(p13;q14)[5]/46,XX, withbalanced reciprocal translocation between the short arm of chromosome 10and the long arm of chromosome 11. Genome molecular profiling showedrecurrent translocation PICALM-MLLT10 [CALM-AF10];t(10;11)(p13;q14) withno disruption of the MLL (11q23) locus, confirming the negative MLL FISHresult. The patient achieved complete remission following phase-twoinduction on the UKALL14 protocol and elected to have a volunteerunrelated donor (VUD) myeloablative allogeneic bone marrow transplant.She remains in complete remission 14 months post-transplant.
Results
The positive outcome for our patient, following allogeneic transplant,reflects similar reports from the UKALLXII/ECOG2993 trial for patientswith the MLLT10 [CALM-AF10];t(10;11)(p13;q14) mutation. The use ofmutational analysis on RT-PCR early in the diagnostic process, in thiscase, allowed prompt detection of a high-risk cytogenetic abnormalityand more accurate risk stratification that guided the decision toproceed to allogeneic transplant.
Conclusion
Early identification of high risk cytogenetic abnormality incorporating mutational analysis using RT -PCR along with immunophenotype, FISH and karyotype help to risk stratify patients for allogeneic bone marrow transplant resulting in successful outcome in patients with in high risk T-ALL.
Session topic: E-poster
Keyword(s): Allogeneic bone marrow transplant, CALM/AF10, T-ALL
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