EVOLUTION OF RUNX1 AND ASXL1 MUTATIONS DURING THE PROGRESSION OF CHRONIC MYELOID LEUKEMIA TO MYELOID BLAST PHASE: AN ANALYSIS OF 52 MATCHED PAIRED SAMPLES AT BOTH INITIAL DIAGNOSIS AND BLAST PHASE
(Abstract release date: 05/19/16)
EHA Library. Kao H. 06/09/16; 132636; E1087
Dr. Hsiao-Wen Kao
Contributions
Contributions
Abstract
Abstract: E1087
Type: Eposter Presentation
Background
Before imatinib era, most patients with Ph-positive chronic myeloid leukemia (CML) diagnosed at chronic phase (CP) or accelerated phase (AP) will transform to blast phase (BP) compared with a small number of patients receiving imatinib therapy. The biology of CML-BP is still largely unknown. Data from direct comparison of matched samples between both diagnosis and BP was limited.
Aims
We aimed to determine the role of RUNX1 and ASXL1 mutations in addition to BCR-ABL1 kinase domain (ABL1-KD) mutations during the progression of CML in a larger cohort of matched paired samples in CP/AP and myeloid BP.
Methods
Bone marrow samples from 52 patients with CML at initial diagnosis (47 CP and 5 AP) and myeloid BP transformation were enrolled. Nineteen patients received imatinib therapy before BP transformation (group A) and the remaining 33 patients had not been treated with imatinib (group B). Semi-nested polymerase chain reaction (PCR) assay followed by denaturing high-performance liquid chromatography and/or direct sequencing was used to detect ABL1-KD mutations. RUNX1 (exons 3-8) and ASXL1 (exon 12) mutations were analyzed by PCR-based assays and direct sequencing. Patients with ABL1-KD, RUNX1, or ASXL1 mutations in myeloid BP were subjected to the analyses of the corresponding genes in the matched diagnosis samples. Pyrosequencing was used to measure the mutant levels.
Results
The median age of patients at the time of CML diagnosis was 45 (16-84) years. The median time from CP/AP to myeloid BP was 26 (1.9-162.9) months. Eight (42.1%, 8/19) of group A patients had ABL1-KD mutations at BP compared with none in group B patients (P = 0.0003). None of the 8 patients carrying ABL1-KD mutations at BP had ABL1-KD mutations detected in the diagnostic samples. Ten (19.2%, 10/52) patients in myeloid BP had RUNX1 mutations, but none of them had RUNX1 mutation in the corresponding diagnostic samples. Only one of the 10 patients with RUNX1 mutations in myeloid BP had ABL1-KD mutations. Two patients (10.5%, 2/19) acquired RUNX1 mutations at BP in group A compared with 24.2% (8/33) in group B (P = 0.227). ASXL1 mutation was detected in 6 (11.8%, 6/51) samples in myeloid BP, of which only one was positive for ASXL1 mutation in the diagnostic sample which was in AP. All the 5 patients who acquired ASXL1 mutations did not have ABL1-KD mutation in myeloid BP. Acquisition of ASXL1 mutations in myeloid BP was 0 % (0/18) and 18.2% (6/33) in group A and group B, respectively (P = 0.054). Together, 3 patients had co-existence of RUNX1 and ASXL1 mutations at myeloid BP. Emergence of ABL1-KD mutations did not significantly affect the acquisition of RUNX1 or ASXL1 mutations during myeloid BP transformation.
Conclusion
RUNX1, ASXL1 or ABL1-KD mutations were not detected in CML patients at initial diagnosis except one who presented with AP. Acquisition of RUNX1 and/or ASXL1 mutations occurred in 25.5% (13/51) of patients during myeloid BP transformation. ABL1-KD mutations only occurred in patients treated with Imatinib, and ASXL1 mutations were prone to develop in patients not treated with Imatinib. (Grant support: XMRPG360366 and OMRPG3C0021)
Session topic: E-poster
Keyword(s): Blast crisis, Chronic myeloid leukemia, Mutation analysis, RUNX1
Type: Eposter Presentation
Background
Before imatinib era, most patients with Ph-positive chronic myeloid leukemia (CML) diagnosed at chronic phase (CP) or accelerated phase (AP) will transform to blast phase (BP) compared with a small number of patients receiving imatinib therapy. The biology of CML-BP is still largely unknown. Data from direct comparison of matched samples between both diagnosis and BP was limited.
Aims
We aimed to determine the role of RUNX1 and ASXL1 mutations in addition to BCR-ABL1 kinase domain (ABL1-KD) mutations during the progression of CML in a larger cohort of matched paired samples in CP/AP and myeloid BP.
Methods
Bone marrow samples from 52 patients with CML at initial diagnosis (47 CP and 5 AP) and myeloid BP transformation were enrolled. Nineteen patients received imatinib therapy before BP transformation (group A) and the remaining 33 patients had not been treated with imatinib (group B). Semi-nested polymerase chain reaction (PCR) assay followed by denaturing high-performance liquid chromatography and/or direct sequencing was used to detect ABL1-KD mutations. RUNX1 (exons 3-8) and ASXL1 (exon 12) mutations were analyzed by PCR-based assays and direct sequencing. Patients with ABL1-KD, RUNX1, or ASXL1 mutations in myeloid BP were subjected to the analyses of the corresponding genes in the matched diagnosis samples. Pyrosequencing was used to measure the mutant levels.
Results
The median age of patients at the time of CML diagnosis was 45 (16-84) years. The median time from CP/AP to myeloid BP was 26 (1.9-162.9) months. Eight (42.1%, 8/19) of group A patients had ABL1-KD mutations at BP compared with none in group B patients (P = 0.0003). None of the 8 patients carrying ABL1-KD mutations at BP had ABL1-KD mutations detected in the diagnostic samples. Ten (19.2%, 10/52) patients in myeloid BP had RUNX1 mutations, but none of them had RUNX1 mutation in the corresponding diagnostic samples. Only one of the 10 patients with RUNX1 mutations in myeloid BP had ABL1-KD mutations. Two patients (10.5%, 2/19) acquired RUNX1 mutations at BP in group A compared with 24.2% (8/33) in group B (P = 0.227). ASXL1 mutation was detected in 6 (11.8%, 6/51) samples in myeloid BP, of which only one was positive for ASXL1 mutation in the diagnostic sample which was in AP. All the 5 patients who acquired ASXL1 mutations did not have ABL1-KD mutation in myeloid BP. Acquisition of ASXL1 mutations in myeloid BP was 0 % (0/18) and 18.2% (6/33) in group A and group B, respectively (P = 0.054). Together, 3 patients had co-existence of RUNX1 and ASXL1 mutations at myeloid BP. Emergence of ABL1-KD mutations did not significantly affect the acquisition of RUNX1 or ASXL1 mutations during myeloid BP transformation.
Conclusion
RUNX1, ASXL1 or ABL1-KD mutations were not detected in CML patients at initial diagnosis except one who presented with AP. Acquisition of RUNX1 and/or ASXL1 mutations occurred in 25.5% (13/51) of patients during myeloid BP transformation. ABL1-KD mutations only occurred in patients treated with Imatinib, and ASXL1 mutations were prone to develop in patients not treated with Imatinib. (Grant support: XMRPG360366 and OMRPG3C0021)
Session topic: E-poster
Keyword(s): Blast crisis, Chronic myeloid leukemia, Mutation analysis, RUNX1
Abstract: E1087
Type: Eposter Presentation
Background
Before imatinib era, most patients with Ph-positive chronic myeloid leukemia (CML) diagnosed at chronic phase (CP) or accelerated phase (AP) will transform to blast phase (BP) compared with a small number of patients receiving imatinib therapy. The biology of CML-BP is still largely unknown. Data from direct comparison of matched samples between both diagnosis and BP was limited.
Aims
We aimed to determine the role of RUNX1 and ASXL1 mutations in addition to BCR-ABL1 kinase domain (ABL1-KD) mutations during the progression of CML in a larger cohort of matched paired samples in CP/AP and myeloid BP.
Methods
Bone marrow samples from 52 patients with CML at initial diagnosis (47 CP and 5 AP) and myeloid BP transformation were enrolled. Nineteen patients received imatinib therapy before BP transformation (group A) and the remaining 33 patients had not been treated with imatinib (group B). Semi-nested polymerase chain reaction (PCR) assay followed by denaturing high-performance liquid chromatography and/or direct sequencing was used to detect ABL1-KD mutations. RUNX1 (exons 3-8) and ASXL1 (exon 12) mutations were analyzed by PCR-based assays and direct sequencing. Patients with ABL1-KD, RUNX1, or ASXL1 mutations in myeloid BP were subjected to the analyses of the corresponding genes in the matched diagnosis samples. Pyrosequencing was used to measure the mutant levels.
Results
The median age of patients at the time of CML diagnosis was 45 (16-84) years. The median time from CP/AP to myeloid BP was 26 (1.9-162.9) months. Eight (42.1%, 8/19) of group A patients had ABL1-KD mutations at BP compared with none in group B patients (P = 0.0003). None of the 8 patients carrying ABL1-KD mutations at BP had ABL1-KD mutations detected in the diagnostic samples. Ten (19.2%, 10/52) patients in myeloid BP had RUNX1 mutations, but none of them had RUNX1 mutation in the corresponding diagnostic samples. Only one of the 10 patients with RUNX1 mutations in myeloid BP had ABL1-KD mutations. Two patients (10.5%, 2/19) acquired RUNX1 mutations at BP in group A compared with 24.2% (8/33) in group B (P = 0.227). ASXL1 mutation was detected in 6 (11.8%, 6/51) samples in myeloid BP, of which only one was positive for ASXL1 mutation in the diagnostic sample which was in AP. All the 5 patients who acquired ASXL1 mutations did not have ABL1-KD mutation in myeloid BP. Acquisition of ASXL1 mutations in myeloid BP was 0 % (0/18) and 18.2% (6/33) in group A and group B, respectively (P = 0.054). Together, 3 patients had co-existence of RUNX1 and ASXL1 mutations at myeloid BP. Emergence of ABL1-KD mutations did not significantly affect the acquisition of RUNX1 or ASXL1 mutations during myeloid BP transformation.
Conclusion
RUNX1, ASXL1 or ABL1-KD mutations were not detected in CML patients at initial diagnosis except one who presented with AP. Acquisition of RUNX1 and/or ASXL1 mutations occurred in 25.5% (13/51) of patients during myeloid BP transformation. ABL1-KD mutations only occurred in patients treated with Imatinib, and ASXL1 mutations were prone to develop in patients not treated with Imatinib. (Grant support: XMRPG360366 and OMRPG3C0021)
Session topic: E-poster
Keyword(s): Blast crisis, Chronic myeloid leukemia, Mutation analysis, RUNX1
Type: Eposter Presentation
Background
Before imatinib era, most patients with Ph-positive chronic myeloid leukemia (CML) diagnosed at chronic phase (CP) or accelerated phase (AP) will transform to blast phase (BP) compared with a small number of patients receiving imatinib therapy. The biology of CML-BP is still largely unknown. Data from direct comparison of matched samples between both diagnosis and BP was limited.
Aims
We aimed to determine the role of RUNX1 and ASXL1 mutations in addition to BCR-ABL1 kinase domain (ABL1-KD) mutations during the progression of CML in a larger cohort of matched paired samples in CP/AP and myeloid BP.
Methods
Bone marrow samples from 52 patients with CML at initial diagnosis (47 CP and 5 AP) and myeloid BP transformation were enrolled. Nineteen patients received imatinib therapy before BP transformation (group A) and the remaining 33 patients had not been treated with imatinib (group B). Semi-nested polymerase chain reaction (PCR) assay followed by denaturing high-performance liquid chromatography and/or direct sequencing was used to detect ABL1-KD mutations. RUNX1 (exons 3-8) and ASXL1 (exon 12) mutations were analyzed by PCR-based assays and direct sequencing. Patients with ABL1-KD, RUNX1, or ASXL1 mutations in myeloid BP were subjected to the analyses of the corresponding genes in the matched diagnosis samples. Pyrosequencing was used to measure the mutant levels.
Results
The median age of patients at the time of CML diagnosis was 45 (16-84) years. The median time from CP/AP to myeloid BP was 26 (1.9-162.9) months. Eight (42.1%, 8/19) of group A patients had ABL1-KD mutations at BP compared with none in group B patients (P = 0.0003). None of the 8 patients carrying ABL1-KD mutations at BP had ABL1-KD mutations detected in the diagnostic samples. Ten (19.2%, 10/52) patients in myeloid BP had RUNX1 mutations, but none of them had RUNX1 mutation in the corresponding diagnostic samples. Only one of the 10 patients with RUNX1 mutations in myeloid BP had ABL1-KD mutations. Two patients (10.5%, 2/19) acquired RUNX1 mutations at BP in group A compared with 24.2% (8/33) in group B (P = 0.227). ASXL1 mutation was detected in 6 (11.8%, 6/51) samples in myeloid BP, of which only one was positive for ASXL1 mutation in the diagnostic sample which was in AP. All the 5 patients who acquired ASXL1 mutations did not have ABL1-KD mutation in myeloid BP. Acquisition of ASXL1 mutations in myeloid BP was 0 % (0/18) and 18.2% (6/33) in group A and group B, respectively (P = 0.054). Together, 3 patients had co-existence of RUNX1 and ASXL1 mutations at myeloid BP. Emergence of ABL1-KD mutations did not significantly affect the acquisition of RUNX1 or ASXL1 mutations during myeloid BP transformation.
Conclusion
RUNX1, ASXL1 or ABL1-KD mutations were not detected in CML patients at initial diagnosis except one who presented with AP. Acquisition of RUNX1 and/or ASXL1 mutations occurred in 25.5% (13/51) of patients during myeloid BP transformation. ABL1-KD mutations only occurred in patients treated with Imatinib, and ASXL1 mutations were prone to develop in patients not treated with Imatinib. (Grant support: XMRPG360366 and OMRPG3C0021)
Session topic: E-poster
Keyword(s): Blast crisis, Chronic myeloid leukemia, Mutation analysis, RUNX1
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