Contributions
Abstract: PB2104
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of bone marrow myeloid cells with impaired differentiation. Studies utilizing next-generation sequencing (NGS) have identified a core set of recurrently mutated genes in the majority of patients with AML and MDS. The identification of recurrent mutations in MDS has led to incipient insights into the pathophysiology of this disorder including those with mundane cytogenetics. DNA-level mutations in several of these genes including ASXL1, ETV6, EZH2, RUNX1 and TP53 in MDS contribute to disease pathogenesis, outcome and currently is an active area of research.
Aims
Our institution is first in the country to perform next generation sequencing analysis. This study is a beginning to the insight of genomics in this disorder with respect to racial difference as much limited has been done on regional level with none reported nationally. With this aim the study was done to assess mutation analysis in MDS and correlate the data with the clinical outcome of the patient.
Methods
A total of 20 MDS diagnosed patients by bone marrow biopsy and cytogenetics were included. Informed consent and detailed history was taken from all patients. The next generation sequencing analysis for a panel of 54 genes including tumor suppressor and oncogenic hotspots associated with myeloid malignancies (AML, MDS, MPN, CMML and JMML) was performed using DNA samples.
Results
A total of 20 MDS patients (14 males and 6 females) meeting the criteria of WHO classification were included. The mean age of the patients was 42 years. Most common presenting complain was weakness in 13 (65%) patients followed by fever and lethargy in 6 (30%). The mean IPSS was 01. Cytogenetic analysis revealed 13(65%) patients with abnormal karyotype while 7(35%) with normal karyotype. Using next generation sequence analysis, 10 (50%) patients had mutations including 2 novel mutations {RUNX1 p.lle428Thr(het) and GATA2 p.Thr358Pro} and 8 reported mutations including p.Pro384Leu (het) RunX1,p. Pro75Leu CDKN2A,Tet-2 c5162 T>G mutation,p.Gln1039Ter (het) ASXL1,p.Gly12Ser , NRAS and DNMT3A NPM. Patients who carried mutations received blood transfusion, lenalidomide, hematinics and azacitidine for treatment. Out of these, 03 patients were transformed into acute myeloid leukemia and received chemotherapy. Mutations in MDS are associated with changes in patient outcomes and it was found statistically significant in our cohort. Numbers of expiry in patients identified with mutations were comparably higher than those who did not carry any mutation (P-value=0.017).
Conclusion
Sequencing studies suggest that multiple mutations are required for MDS initiation and progression to acute myeloid leukemia (AML). In addition to providing prognostic information, these gene mutations can be used to monitor patient disease burden through the use of ultrasensitive detection techniques like NGS. The past several years have yielded many incipient insights, but the consummate genetic landscape of MDS is not yet kenned. Additional studies will be required to understand the prognostic implications of these mutations for treatment, disease progression and survival.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Cytogenetics, MDS, Mutation, Outcome
Abstract: PB2104
Type: Publication Only
Background
Myelodysplastic syndromes (MDS) are a heterogenous group of hematologic malignancies characterized by clonal expansion of bone marrow myeloid cells with impaired differentiation. Studies utilizing next-generation sequencing (NGS) have identified a core set of recurrently mutated genes in the majority of patients with AML and MDS. The identification of recurrent mutations in MDS has led to incipient insights into the pathophysiology of this disorder including those with mundane cytogenetics. DNA-level mutations in several of these genes including ASXL1, ETV6, EZH2, RUNX1 and TP53 in MDS contribute to disease pathogenesis, outcome and currently is an active area of research.
Aims
Our institution is first in the country to perform next generation sequencing analysis. This study is a beginning to the insight of genomics in this disorder with respect to racial difference as much limited has been done on regional level with none reported nationally. With this aim the study was done to assess mutation analysis in MDS and correlate the data with the clinical outcome of the patient.
Methods
A total of 20 MDS diagnosed patients by bone marrow biopsy and cytogenetics were included. Informed consent and detailed history was taken from all patients. The next generation sequencing analysis for a panel of 54 genes including tumor suppressor and oncogenic hotspots associated with myeloid malignancies (AML, MDS, MPN, CMML and JMML) was performed using DNA samples.
Results
A total of 20 MDS patients (14 males and 6 females) meeting the criteria of WHO classification were included. The mean age of the patients was 42 years. Most common presenting complain was weakness in 13 (65%) patients followed by fever and lethargy in 6 (30%). The mean IPSS was 01. Cytogenetic analysis revealed 13(65%) patients with abnormal karyotype while 7(35%) with normal karyotype. Using next generation sequence analysis, 10 (50%) patients had mutations including 2 novel mutations {RUNX1 p.lle428Thr(het) and GATA2 p.Thr358Pro} and 8 reported mutations including p.Pro384Leu (het) RunX1,p. Pro75Leu CDKN2A,Tet-2 c5162 T>G mutation,p.Gln1039Ter (het) ASXL1,p.Gly12Ser , NRAS and DNMT3A NPM. Patients who carried mutations received blood transfusion, lenalidomide, hematinics and azacitidine for treatment. Out of these, 03 patients were transformed into acute myeloid leukemia and received chemotherapy. Mutations in MDS are associated with changes in patient outcomes and it was found statistically significant in our cohort. Numbers of expiry in patients identified with mutations were comparably higher than those who did not carry any mutation (P-value=0.017).
Conclusion
Sequencing studies suggest that multiple mutations are required for MDS initiation and progression to acute myeloid leukemia (AML). In addition to providing prognostic information, these gene mutations can be used to monitor patient disease burden through the use of ultrasensitive detection techniques like NGS. The past several years have yielded many incipient insights, but the consummate genetic landscape of MDS is not yet kenned. Additional studies will be required to understand the prognostic implications of these mutations for treatment, disease progression and survival.
Session topic: 10. Myelodysplastic syndromes – Clinical
Keyword(s): Cytogenetics, MDS, Mutation, Outcome