CLINICAL IMPLICATIONS OF MYD88 L265P MUTATION IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
(Abstract release date: 05/19/16)
EHA Library. Sidorova A. 06/09/16; 134941; PB2041
Ms. Anna Sidorova
Contributions
Contributions
Abstract
Abstract: PB2041
Type: Publication Only
Background
It is now well known fact that recurrent mutation in the MYD88 gene (L265P MYD88) is identified in about 90% of Waldenström macroglobulinemia, in approximately one-quarter of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and in a minority of cases of other lymphoproliferative disorders. Evidence is beginning to accumulate that L265P MYD88 mutation in pts with DLBCL has strong association with clinical phenotypes and outcomes.
Aims
To evaluate the clinical implications of MYD88 L265P mutation in pts with DLBCL.
Methods
We analyzed the data of 75 pts (median age 50 years, range 18-77, 33/42 female/male ratio, 39 extranodal and 36 nodal disease) with de novo DLBCL diagnosed between 1999 to 2015 at National Research Center for Hematology. Pts were classified as germinal center B-cell-like (GCB) or non-GCB DLBCL using the Hans algorithm. For molecular analysis DNA was extracted from 56 cryopreserved and 19 formalin-fixed paraffin-embedded tumor tissue. The mutational status of a sample was determined by real-time PCR (RT-PCR).
Results
MYD88 L265P mutation was detected in 14(18,7%) out of 75 pts. Half of pts with MYD88-positive MYD88 L265P mutation DLBCL are older than 60 years compared with only 24,6% of those pts with MYD88 unmutated DLBCL. In terms of sex ratio the data show a double preponderance of males at MYD88 L265P positive DLBCL (9:5) as compared with MYD88 wild type DLBCL with the same number of males and females (33:28). There was equal distribution of pts across high-intermediate and high risk groups of the international prognostic index both in MYD88 mutated and MYD88 unmutated pts (71,7% vs 63,9%). The majority of pts in both groups had elevated serum lactate dehydrogenase levels, 12/14 (85,7%) and 47/61 (77%) respectively. Tumors with high Ki-67>80% expression were found in 13(92,8%) of pts MYD88 mutation versus 43(70,5%) pts with MYD88 wild type DLBCL. All 14(100%) pts with MYD88 L265P DLBCL were non-GCB DLBCL as compared to 42/61(72%) pts with MYD88 unmutated DLBCL. Eleven (78,6%) out of 14 pts with MYD88 mutation had extranodal lesions (р<0,05). Five (45,4%) of 11 cases MYD88 L265P extranodal DLBCL were present in immune-privileged site DLBCL (central nervous system, testis) versus 4(14,2%) out of 28 pts with MYD88 wild type extranodal DLBCL (р<0,05). The table summarizes baseline characteristics pts.
Conclusion
It is apparent from the present study that MYD88 L265P mutation was significantly associated with extranodal DLBCL (78,6%) and prevalent in immune-privileged site DLBCL. Detection of MYD88 L265P mutation by RT-PCR could improve diagnosis non-GCB DLBCL as a complement to immunohistochemistry.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, Mutation
Type: Publication Only
Background
It is now well known fact that recurrent mutation in the MYD88 gene (L265P MYD88) is identified in about 90% of Waldenström macroglobulinemia, in approximately one-quarter of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and in a minority of cases of other lymphoproliferative disorders. Evidence is beginning to accumulate that L265P MYD88 mutation in pts with DLBCL has strong association with clinical phenotypes and outcomes.
Aims
To evaluate the clinical implications of MYD88 L265P mutation in pts with DLBCL.
Methods
We analyzed the data of 75 pts (median age 50 years, range 18-77, 33/42 female/male ratio, 39 extranodal and 36 nodal disease) with de novo DLBCL diagnosed between 1999 to 2015 at National Research Center for Hematology. Pts were classified as germinal center B-cell-like (GCB) or non-GCB DLBCL using the Hans algorithm. For molecular analysis DNA was extracted from 56 cryopreserved and 19 formalin-fixed paraffin-embedded tumor tissue. The mutational status of a sample was determined by real-time PCR (RT-PCR).
Results
MYD88 L265P mutation was detected in 14(18,7%) out of 75 pts. Half of pts with MYD88-positive MYD88 L265P mutation DLBCL are older than 60 years compared with only 24,6% of those pts with MYD88 unmutated DLBCL. In terms of sex ratio the data show a double preponderance of males at MYD88 L265P positive DLBCL (9:5) as compared with MYD88 wild type DLBCL with the same number of males and females (33:28). There was equal distribution of pts across high-intermediate and high risk groups of the international prognostic index both in MYD88 mutated and MYD88 unmutated pts (71,7% vs 63,9%). The majority of pts in both groups had elevated serum lactate dehydrogenase levels, 12/14 (85,7%) and 47/61 (77%) respectively. Tumors with high Ki-67>80% expression were found in 13(92,8%) of pts MYD88 mutation versus 43(70,5%) pts with MYD88 wild type DLBCL. All 14(100%) pts with MYD88 L265P DLBCL were non-GCB DLBCL as compared to 42/61(72%) pts with MYD88 unmutated DLBCL. Eleven (78,6%) out of 14 pts with MYD88 mutation had extranodal lesions (р<0,05). Five (45,4%) of 11 cases MYD88 L265P extranodal DLBCL were present in immune-privileged site DLBCL (central nervous system, testis) versus 4(14,2%) out of 28 pts with MYD88 wild type extranodal DLBCL (р<0,05). The table summarizes baseline characteristics pts.
Conclusion
It is apparent from the present study that MYD88 L265P mutation was significantly associated with extranodal DLBCL (78,6%) and prevalent in immune-privileged site DLBCL. Detection of MYD88 L265P mutation by RT-PCR could improve diagnosis non-GCB DLBCL as a complement to immunohistochemistry.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, Mutation
Abstract: PB2041
Type: Publication Only
Background
It is now well known fact that recurrent mutation in the MYD88 gene (L265P MYD88) is identified in about 90% of Waldenström macroglobulinemia, in approximately one-quarter of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and in a minority of cases of other lymphoproliferative disorders. Evidence is beginning to accumulate that L265P MYD88 mutation in pts with DLBCL has strong association with clinical phenotypes and outcomes.
Aims
To evaluate the clinical implications of MYD88 L265P mutation in pts with DLBCL.
Methods
We analyzed the data of 75 pts (median age 50 years, range 18-77, 33/42 female/male ratio, 39 extranodal and 36 nodal disease) with de novo DLBCL diagnosed between 1999 to 2015 at National Research Center for Hematology. Pts were classified as germinal center B-cell-like (GCB) or non-GCB DLBCL using the Hans algorithm. For molecular analysis DNA was extracted from 56 cryopreserved and 19 formalin-fixed paraffin-embedded tumor tissue. The mutational status of a sample was determined by real-time PCR (RT-PCR).
Results
MYD88 L265P mutation was detected in 14(18,7%) out of 75 pts. Half of pts with MYD88-positive MYD88 L265P mutation DLBCL are older than 60 years compared with only 24,6% of those pts with MYD88 unmutated DLBCL. In terms of sex ratio the data show a double preponderance of males at MYD88 L265P positive DLBCL (9:5) as compared with MYD88 wild type DLBCL with the same number of males and females (33:28). There was equal distribution of pts across high-intermediate and high risk groups of the international prognostic index both in MYD88 mutated and MYD88 unmutated pts (71,7% vs 63,9%). The majority of pts in both groups had elevated serum lactate dehydrogenase levels, 12/14 (85,7%) and 47/61 (77%) respectively. Tumors with high Ki-67>80% expression were found in 13(92,8%) of pts MYD88 mutation versus 43(70,5%) pts with MYD88 wild type DLBCL. All 14(100%) pts with MYD88 L265P DLBCL were non-GCB DLBCL as compared to 42/61(72%) pts with MYD88 unmutated DLBCL. Eleven (78,6%) out of 14 pts with MYD88 mutation had extranodal lesions (р<0,05). Five (45,4%) of 11 cases MYD88 L265P extranodal DLBCL were present in immune-privileged site DLBCL (central nervous system, testis) versus 4(14,2%) out of 28 pts with MYD88 wild type extranodal DLBCL (р<0,05). The table summarizes baseline characteristics pts.
Conclusion
It is apparent from the present study that MYD88 L265P mutation was significantly associated with extranodal DLBCL (78,6%) and prevalent in immune-privileged site DLBCL. Detection of MYD88 L265P mutation by RT-PCR could improve diagnosis non-GCB DLBCL as a complement to immunohistochemistry.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, Mutation
Type: Publication Only
Background
It is now well known fact that recurrent mutation in the MYD88 gene (L265P MYD88) is identified in about 90% of Waldenström macroglobulinemia, in approximately one-quarter of patients (pts) with diffuse large B-cell lymphoma (DLBCL) and in a minority of cases of other lymphoproliferative disorders. Evidence is beginning to accumulate that L265P MYD88 mutation in pts with DLBCL has strong association with clinical phenotypes and outcomes.
Aims
To evaluate the clinical implications of MYD88 L265P mutation in pts with DLBCL.
Methods
We analyzed the data of 75 pts (median age 50 years, range 18-77, 33/42 female/male ratio, 39 extranodal and 36 nodal disease) with de novo DLBCL diagnosed between 1999 to 2015 at National Research Center for Hematology. Pts were classified as germinal center B-cell-like (GCB) or non-GCB DLBCL using the Hans algorithm. For molecular analysis DNA was extracted from 56 cryopreserved and 19 formalin-fixed paraffin-embedded tumor tissue. The mutational status of a sample was determined by real-time PCR (RT-PCR).
Results
MYD88 L265P mutation was detected in 14(18,7%) out of 75 pts. Half of pts with MYD88-positive MYD88 L265P mutation DLBCL are older than 60 years compared with only 24,6% of those pts with MYD88 unmutated DLBCL. In terms of sex ratio the data show a double preponderance of males at MYD88 L265P positive DLBCL (9:5) as compared with MYD88 wild type DLBCL with the same number of males and females (33:28). There was equal distribution of pts across high-intermediate and high risk groups of the international prognostic index both in MYD88 mutated and MYD88 unmutated pts (71,7% vs 63,9%). The majority of pts in both groups had elevated serum lactate dehydrogenase levels, 12/14 (85,7%) and 47/61 (77%) respectively. Tumors with high Ki-67>80% expression were found in 13(92,8%) of pts MYD88 mutation versus 43(70,5%) pts with MYD88 wild type DLBCL. All 14(100%) pts with MYD88 L265P DLBCL were non-GCB DLBCL as compared to 42/61(72%) pts with MYD88 unmutated DLBCL. Eleven (78,6%) out of 14 pts with MYD88 mutation had extranodal lesions (р<0,05). Five (45,4%) of 11 cases MYD88 L265P extranodal DLBCL were present in immune-privileged site DLBCL (central nervous system, testis) versus 4(14,2%) out of 28 pts with MYD88 wild type extranodal DLBCL (р<0,05). The table summarizes baseline characteristics pts.
Conclusion
It is apparent from the present study that MYD88 L265P mutation was significantly associated with extranodal DLBCL (78,6%) and prevalent in immune-privileged site DLBCL. Detection of MYD88 L265P mutation by RT-PCR could improve diagnosis non-GCB DLBCL as a complement to immunohistochemistry.
Session topic: E-poster
Keyword(s): Diffuse large B cell lymphoma, Mutation
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