DETECTION OF BASOPHIL-ASSOCIATED IMMUNOPHENOTYPIC FEATURES OF ACUTE PROMYELOCYTIC LEUKEMIA BLAST CELLS AT DIAGNOSIS IS ASSOCIATED TO A HIGHER AND MORE SEVERE BLEEDING DIATHESIS
(Abstract release date: 05/19/16)
EHA Library. Orfao A. 06/09/16; 132480; E931
Prof. Dr. Alberto Orfao
Contributions
Contributions
Abstract
Abstract: E931
Type: Eposter Presentation
Background
The introduction of induction therapy with all-trans retinoic acid and anthracycline-based chemotherapy in acute promyelocytic leukemia (APL) have translated into complete remission in most patients. However, severe hemorrhage manifestations at diagnosis and/or during induction therapy lead to early death in 10-15% of patients, which is currently a major focus of research in APL.
Aims
Here we performed an extensive immunophenotypic characterization of blast cells from APL and investigated the potential association between their differential phenotypic profiles and the bleeding diathesis depicted at baseline.
Methods
A total of 133 bone marrow samples from newly-diagnosed APL patients were immunophenotypically characterized. In all cases, 8-color flow cytometry was performed for in depth characterization of APL blast cells and residual hematopoietic cell compartments using the EuroFlow AML/MDS panel. The relatioship between the bleeding diathesis and the immunophenotypic features of blast cells at diagnosis could be studied in 86 APL cases.
Results
The multiparameter immunophenotypic characterization of marrow APL blast cells revealed that these patientes systematically depict (among 100% of their leukemic cells) CyMPO+/++, CD33+/hi, and CD123+/hi expression, together with CD15-/low CD117+, CD71+ and CD9+, while lacking the myelomonocytic maturing-associated markers CD16, CD10 and CD300e, as well as the expression of CD105, NG2 (7.1), CD25 and the megakaryocytic lineage-associated markers CD41, CD61, CD42a, CD42b. Other (aberrant) phenotypes were typically found in APL although at lower frequency, including CD64low (55/59 cases; 93%), HLA-DR- (72/78; 92%), CD13+/++ (56/61; 92%) and CD38+ (47/55; 86%), followed by CD4low (30/58 cases; 52%), CD203c+ (40/92; 44%), CD34+ (23/78; 30%), the cross-lineage expression of CD7 (14/47; 30%), asynchronous reactivity for CD35 (14/52; 27%) and CD22 (8/52; 15%) and ectopic CD56 (9/60 cases; 15%). The expression of several other markers was rather exceptional in APL blast cells, including, CD19 (7/58 cases; 12%), CD79a (6/57; 10%), CD14, NuTdT (3/54; 5%), CD11b (2/59; 3%) and CD36 (2/61; 1%). Of note, from all analyzed markers the expression vs. lack of CD203c showed the strongest association with bleeding manifestations at diagnosis (90% vs. 10% of APL cases; p<0.001), followed by CD7 (89% vs. 11%; p=0.03), CyCD79a (0% vs. 100%; p=0.05) and a similar trend for the expression of CD34 by blast cells (74% vs. 26%; p=0.06). Furthermore, APL cases with severe bleeding at diagnosis depicted a significantly higher frequency of CD203 expression by blast cells, as compared to those with mild and absent bleeding symptoms at baseline (80% vs. 46% and 10%, respectively; p<0.001). A similar association was respectively found for the expression of CD7 by blast cells (75% vs. 31% and 7%; p=0.02) and cytoplasmic CD79a (33% vs. 18% and 0%; p=0.05).
Conclusion
The presence of basophil differentiation features in marrow APL blast cells, as depicted by their expression of CD203c and/or CD22, and to a lower extent also of certain cross-lineage antigen expression markers (CD7 and/or CD79a) is associated to a higher frequency and severity of bleeding symptoms at diagnosis, which might point to the need of adapted therapy protocols particularly in these cases.
Session topic: E-poster
Keyword(s): Bleeding, Flow cytometry, Immunophenotype
Type: Eposter Presentation
Background
The introduction of induction therapy with all-trans retinoic acid and anthracycline-based chemotherapy in acute promyelocytic leukemia (APL) have translated into complete remission in most patients. However, severe hemorrhage manifestations at diagnosis and/or during induction therapy lead to early death in 10-15% of patients, which is currently a major focus of research in APL.
Aims
Here we performed an extensive immunophenotypic characterization of blast cells from APL and investigated the potential association between their differential phenotypic profiles and the bleeding diathesis depicted at baseline.
Methods
A total of 133 bone marrow samples from newly-diagnosed APL patients were immunophenotypically characterized. In all cases, 8-color flow cytometry was performed for in depth characterization of APL blast cells and residual hematopoietic cell compartments using the EuroFlow AML/MDS panel. The relatioship between the bleeding diathesis and the immunophenotypic features of blast cells at diagnosis could be studied in 86 APL cases.
Results
The multiparameter immunophenotypic characterization of marrow APL blast cells revealed that these patientes systematically depict (among 100% of their leukemic cells) CyMPO+/++, CD33+/hi, and CD123+/hi expression, together with CD15-/low CD117+, CD71+ and CD9+, while lacking the myelomonocytic maturing-associated markers CD16, CD10 and CD300e, as well as the expression of CD105, NG2 (7.1), CD25 and the megakaryocytic lineage-associated markers CD41, CD61, CD42a, CD42b. Other (aberrant) phenotypes were typically found in APL although at lower frequency, including CD64low (55/59 cases; 93%), HLA-DR- (72/78; 92%), CD13+/++ (56/61; 92%) and CD38+ (47/55; 86%), followed by CD4low (30/58 cases; 52%), CD203c+ (40/92; 44%), CD34+ (23/78; 30%), the cross-lineage expression of CD7 (14/47; 30%), asynchronous reactivity for CD35 (14/52; 27%) and CD22 (8/52; 15%) and ectopic CD56 (9/60 cases; 15%). The expression of several other markers was rather exceptional in APL blast cells, including, CD19 (7/58 cases; 12%), CD79a (6/57; 10%), CD14, NuTdT (3/54; 5%), CD11b (2/59; 3%) and CD36 (2/61; 1%). Of note, from all analyzed markers the expression vs. lack of CD203c showed the strongest association with bleeding manifestations at diagnosis (90% vs. 10% of APL cases; p<0.001), followed by CD7 (89% vs. 11%; p=0.03), CyCD79a (0% vs. 100%; p=0.05) and a similar trend for the expression of CD34 by blast cells (74% vs. 26%; p=0.06). Furthermore, APL cases with severe bleeding at diagnosis depicted a significantly higher frequency of CD203 expression by blast cells, as compared to those with mild and absent bleeding symptoms at baseline (80% vs. 46% and 10%, respectively; p<0.001). A similar association was respectively found for the expression of CD7 by blast cells (75% vs. 31% and 7%; p=0.02) and cytoplasmic CD79a (33% vs. 18% and 0%; p=0.05).
Conclusion
The presence of basophil differentiation features in marrow APL blast cells, as depicted by their expression of CD203c and/or CD22, and to a lower extent also of certain cross-lineage antigen expression markers (CD7 and/or CD79a) is associated to a higher frequency and severity of bleeding symptoms at diagnosis, which might point to the need of adapted therapy protocols particularly in these cases.
Session topic: E-poster
Keyword(s): Bleeding, Flow cytometry, Immunophenotype
Abstract: E931
Type: Eposter Presentation
Background
The introduction of induction therapy with all-trans retinoic acid and anthracycline-based chemotherapy in acute promyelocytic leukemia (APL) have translated into complete remission in most patients. However, severe hemorrhage manifestations at diagnosis and/or during induction therapy lead to early death in 10-15% of patients, which is currently a major focus of research in APL.
Aims
Here we performed an extensive immunophenotypic characterization of blast cells from APL and investigated the potential association between their differential phenotypic profiles and the bleeding diathesis depicted at baseline.
Methods
A total of 133 bone marrow samples from newly-diagnosed APL patients were immunophenotypically characterized. In all cases, 8-color flow cytometry was performed for in depth characterization of APL blast cells and residual hematopoietic cell compartments using the EuroFlow AML/MDS panel. The relatioship between the bleeding diathesis and the immunophenotypic features of blast cells at diagnosis could be studied in 86 APL cases.
Results
The multiparameter immunophenotypic characterization of marrow APL blast cells revealed that these patientes systematically depict (among 100% of their leukemic cells) CyMPO+/++, CD33+/hi, and CD123+/hi expression, together with CD15-/low CD117+, CD71+ and CD9+, while lacking the myelomonocytic maturing-associated markers CD16, CD10 and CD300e, as well as the expression of CD105, NG2 (7.1), CD25 and the megakaryocytic lineage-associated markers CD41, CD61, CD42a, CD42b. Other (aberrant) phenotypes were typically found in APL although at lower frequency, including CD64low (55/59 cases; 93%), HLA-DR- (72/78; 92%), CD13+/++ (56/61; 92%) and CD38+ (47/55; 86%), followed by CD4low (30/58 cases; 52%), CD203c+ (40/92; 44%), CD34+ (23/78; 30%), the cross-lineage expression of CD7 (14/47; 30%), asynchronous reactivity for CD35 (14/52; 27%) and CD22 (8/52; 15%) and ectopic CD56 (9/60 cases; 15%). The expression of several other markers was rather exceptional in APL blast cells, including, CD19 (7/58 cases; 12%), CD79a (6/57; 10%), CD14, NuTdT (3/54; 5%), CD11b (2/59; 3%) and CD36 (2/61; 1%). Of note, from all analyzed markers the expression vs. lack of CD203c showed the strongest association with bleeding manifestations at diagnosis (90% vs. 10% of APL cases; p<0.001), followed by CD7 (89% vs. 11%; p=0.03), CyCD79a (0% vs. 100%; p=0.05) and a similar trend for the expression of CD34 by blast cells (74% vs. 26%; p=0.06). Furthermore, APL cases with severe bleeding at diagnosis depicted a significantly higher frequency of CD203 expression by blast cells, as compared to those with mild and absent bleeding symptoms at baseline (80% vs. 46% and 10%, respectively; p<0.001). A similar association was respectively found for the expression of CD7 by blast cells (75% vs. 31% and 7%; p=0.02) and cytoplasmic CD79a (33% vs. 18% and 0%; p=0.05).
Conclusion
The presence of basophil differentiation features in marrow APL blast cells, as depicted by their expression of CD203c and/or CD22, and to a lower extent also of certain cross-lineage antigen expression markers (CD7 and/or CD79a) is associated to a higher frequency and severity of bleeding symptoms at diagnosis, which might point to the need of adapted therapy protocols particularly in these cases.
Session topic: E-poster
Keyword(s): Bleeding, Flow cytometry, Immunophenotype
Type: Eposter Presentation
Background
The introduction of induction therapy with all-trans retinoic acid and anthracycline-based chemotherapy in acute promyelocytic leukemia (APL) have translated into complete remission in most patients. However, severe hemorrhage manifestations at diagnosis and/or during induction therapy lead to early death in 10-15% of patients, which is currently a major focus of research in APL.
Aims
Here we performed an extensive immunophenotypic characterization of blast cells from APL and investigated the potential association between their differential phenotypic profiles and the bleeding diathesis depicted at baseline.
Methods
A total of 133 bone marrow samples from newly-diagnosed APL patients were immunophenotypically characterized. In all cases, 8-color flow cytometry was performed for in depth characterization of APL blast cells and residual hematopoietic cell compartments using the EuroFlow AML/MDS panel. The relatioship between the bleeding diathesis and the immunophenotypic features of blast cells at diagnosis could be studied in 86 APL cases.
Results
The multiparameter immunophenotypic characterization of marrow APL blast cells revealed that these patientes systematically depict (among 100% of their leukemic cells) CyMPO+/++, CD33+/hi, and CD123+/hi expression, together with CD15-/low CD117+, CD71+ and CD9+, while lacking the myelomonocytic maturing-associated markers CD16, CD10 and CD300e, as well as the expression of CD105, NG2 (7.1), CD25 and the megakaryocytic lineage-associated markers CD41, CD61, CD42a, CD42b. Other (aberrant) phenotypes were typically found in APL although at lower frequency, including CD64low (55/59 cases; 93%), HLA-DR- (72/78; 92%), CD13+/++ (56/61; 92%) and CD38+ (47/55; 86%), followed by CD4low (30/58 cases; 52%), CD203c+ (40/92; 44%), CD34+ (23/78; 30%), the cross-lineage expression of CD7 (14/47; 30%), asynchronous reactivity for CD35 (14/52; 27%) and CD22 (8/52; 15%) and ectopic CD56 (9/60 cases; 15%). The expression of several other markers was rather exceptional in APL blast cells, including, CD19 (7/58 cases; 12%), CD79a (6/57; 10%), CD14, NuTdT (3/54; 5%), CD11b (2/59; 3%) and CD36 (2/61; 1%). Of note, from all analyzed markers the expression vs. lack of CD203c showed the strongest association with bleeding manifestations at diagnosis (90% vs. 10% of APL cases; p<0.001), followed by CD7 (89% vs. 11%; p=0.03), CyCD79a (0% vs. 100%; p=0.05) and a similar trend for the expression of CD34 by blast cells (74% vs. 26%; p=0.06). Furthermore, APL cases with severe bleeding at diagnosis depicted a significantly higher frequency of CD203 expression by blast cells, as compared to those with mild and absent bleeding symptoms at baseline (80% vs. 46% and 10%, respectively; p<0.001). A similar association was respectively found for the expression of CD7 by blast cells (75% vs. 31% and 7%; p=0.02) and cytoplasmic CD79a (33% vs. 18% and 0%; p=0.05).
Conclusion
The presence of basophil differentiation features in marrow APL blast cells, as depicted by their expression of CD203c and/or CD22, and to a lower extent also of certain cross-lineage antigen expression markers (CD7 and/or CD79a) is associated to a higher frequency and severity of bleeding symptoms at diagnosis, which might point to the need of adapted therapy protocols particularly in these cases.
Session topic: E-poster
Keyword(s): Bleeding, Flow cytometry, Immunophenotype
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