CALRETICULIN GENE MUTATION IN HAIRY CELL LEUKEMIA AND RELATIONSHIP WITH PROGNOSIS
(Abstract release date: 05/19/16)
EHA Library. Subari S. 06/09/16; 134696; PB1796
Dr. Salih Subari
Contributions
Contributions
Abstract
Abstract: PB1796
Type: Publication Only
Background
Hairy cell leukemia (HCL) is a malignant hematologic neoplasm characterized by peripheral blood and bone marrow hairy cells. Etiology of disease is not clear. Calreticulin (CRT) is a protein located on endoplasmic reticulum which plays role on protein folding, calcium homeostasis, regulation and loading antigenic peptides into major histocompatibility class-I in the cells. As of today, CRT gene mutations were determined in JAK2 and MPL negative myeloproliferative neoplasms. However, the effect of this gene mutation on hairy cell leukemia which is a lymphoproliferative disease is unknown.
Aims
To study the presence of CRT mutations in hairy cell leukemia and effects.
Methods
A retrospective single institution study chart review of cases with HCL at Gaziantep University between 2005- 2015 was performed. Patients with precise hairy cell leukemia were included. Bone marrow tissue biopsy samples were used. Following the isolation of genetic material and gene sequence analysis by PCR, mutations were investigated for CRT. Complete blood count, peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry were used to diagnose HCL patients. Laboratory counts were determined as anemia <12g/dL, thrombocytopenia <100x109/L, neutropenia <1 x109/L and monocytopenia <0.2 x109/L. We used French Society of Hematology remission criteria for treated hairy cell leukemia. Appropriate ethics approval approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Mann Whitney U, while survival estimates were calculated using Kaplan-Meier curves SPSS V22.
Results
Out of 33 HCL samples, 21 (63.6%) CRT exon-9 sequencing analyses could be performed and CRT gene mutation was not detected in any. In the clinical analysis of these patients median age was 54 years, with 26 (78.8%) patients were males. Labs at diagnose included median white blood cell was 2.7 x109, Hemoglobin 9.5 g/dL, platelet 58 x109, monocytes 0.28x109, lymphocyte 1.3 x109, neutrophil 1 x109. Laboratory count were found anemia in 22 (%73.3), trombocytopenia in 21 (70%), neutropenia in 14 (48.3%) and monocytopenia in 12 (41.4%) of patients. Out of 33 patients, 27 (90%) had splenomegaly documented at the time of diagnosis. When evaluated pretreatment splenic size by ultrasound, median spleen size was 20.3 centimeter (median %25-75, 16.5-24). Cladribine was used in the treatment of 23 (69.7%) patients. Among these patients’ complete response was 13 (56,5%), partial response was 3 (13%) and overall response was 69.5%. Splenomegaly was significantly high in patients without monocytopenia (p=0.05). There were survival differences between treated (n=23) and untreated (n=10) patient groups (85.6±3 and 17.7±7.8 median months, respectively p=0.001). The patients who treated had significantly longer overall survival compared to those untreated. Furthermore, pretreatment median hemoglobin level was higher in remission group compared to no remission group as 10.1 g/dL vs 8.5 g/dL respectively and there was a statistically significant difference between them (p=0.047).
Conclusion
This is the first study carried out regarding CRT gene mutation in HCL in the literature. We consider that CRT gene mutations are not effective on disease pathogenesis. As a result, spleen size was larger in patients with who had no monocytopenia and initial hemoglobin levels were higher in remission group. This result may be an important finding in terms of timing of treatment in patients with HCL. In this respect, it may be appropriate approach to start to the treatment before anemia develops. Additional larger studies are needed to confirm our results.
Session topic: E-poster
Keyword(s): Anemia, Hairy cell leukemia, Mutation analysis, Spleen
Type: Publication Only
Background
Hairy cell leukemia (HCL) is a malignant hematologic neoplasm characterized by peripheral blood and bone marrow hairy cells. Etiology of disease is not clear. Calreticulin (CRT) is a protein located on endoplasmic reticulum which plays role on protein folding, calcium homeostasis, regulation and loading antigenic peptides into major histocompatibility class-I in the cells. As of today, CRT gene mutations were determined in JAK2 and MPL negative myeloproliferative neoplasms. However, the effect of this gene mutation on hairy cell leukemia which is a lymphoproliferative disease is unknown.
Aims
To study the presence of CRT mutations in hairy cell leukemia and effects.
Methods
A retrospective single institution study chart review of cases with HCL at Gaziantep University between 2005- 2015 was performed. Patients with precise hairy cell leukemia were included. Bone marrow tissue biopsy samples were used. Following the isolation of genetic material and gene sequence analysis by PCR, mutations were investigated for CRT. Complete blood count, peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry were used to diagnose HCL patients. Laboratory counts were determined as anemia <12g/dL, thrombocytopenia <100x109/L, neutropenia <1 x109/L and monocytopenia <0.2 x109/L. We used French Society of Hematology remission criteria for treated hairy cell leukemia. Appropriate ethics approval approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Mann Whitney U, while survival estimates were calculated using Kaplan-Meier curves SPSS V22.
Results
Out of 33 HCL samples, 21 (63.6%) CRT exon-9 sequencing analyses could be performed and CRT gene mutation was not detected in any. In the clinical analysis of these patients median age was 54 years, with 26 (78.8%) patients were males. Labs at diagnose included median white blood cell was 2.7 x109, Hemoglobin 9.5 g/dL, platelet 58 x109, monocytes 0.28x109, lymphocyte 1.3 x109, neutrophil 1 x109. Laboratory count were found anemia in 22 (%73.3), trombocytopenia in 21 (70%), neutropenia in 14 (48.3%) and monocytopenia in 12 (41.4%) of patients. Out of 33 patients, 27 (90%) had splenomegaly documented at the time of diagnosis. When evaluated pretreatment splenic size by ultrasound, median spleen size was 20.3 centimeter (median %25-75, 16.5-24). Cladribine was used in the treatment of 23 (69.7%) patients. Among these patients’ complete response was 13 (56,5%), partial response was 3 (13%) and overall response was 69.5%. Splenomegaly was significantly high in patients without monocytopenia (p=0.05). There were survival differences between treated (n=23) and untreated (n=10) patient groups (85.6±3 and 17.7±7.8 median months, respectively p=0.001). The patients who treated had significantly longer overall survival compared to those untreated. Furthermore, pretreatment median hemoglobin level was higher in remission group compared to no remission group as 10.1 g/dL vs 8.5 g/dL respectively and there was a statistically significant difference between them (p=0.047).
Conclusion
This is the first study carried out regarding CRT gene mutation in HCL in the literature. We consider that CRT gene mutations are not effective on disease pathogenesis. As a result, spleen size was larger in patients with who had no monocytopenia and initial hemoglobin levels were higher in remission group. This result may be an important finding in terms of timing of treatment in patients with HCL. In this respect, it may be appropriate approach to start to the treatment before anemia develops. Additional larger studies are needed to confirm our results.
Session topic: E-poster
Keyword(s): Anemia, Hairy cell leukemia, Mutation analysis, Spleen
Abstract: PB1796
Type: Publication Only
Background
Hairy cell leukemia (HCL) is a malignant hematologic neoplasm characterized by peripheral blood and bone marrow hairy cells. Etiology of disease is not clear. Calreticulin (CRT) is a protein located on endoplasmic reticulum which plays role on protein folding, calcium homeostasis, regulation and loading antigenic peptides into major histocompatibility class-I in the cells. As of today, CRT gene mutations were determined in JAK2 and MPL negative myeloproliferative neoplasms. However, the effect of this gene mutation on hairy cell leukemia which is a lymphoproliferative disease is unknown.
Aims
To study the presence of CRT mutations in hairy cell leukemia and effects.
Methods
A retrospective single institution study chart review of cases with HCL at Gaziantep University between 2005- 2015 was performed. Patients with precise hairy cell leukemia were included. Bone marrow tissue biopsy samples were used. Following the isolation of genetic material and gene sequence analysis by PCR, mutations were investigated for CRT. Complete blood count, peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry were used to diagnose HCL patients. Laboratory counts were determined as anemia <12g/dL, thrombocytopenia <100x109/L, neutropenia <1 x109/L and monocytopenia <0.2 x109/L. We used French Society of Hematology remission criteria for treated hairy cell leukemia. Appropriate ethics approval approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Mann Whitney U, while survival estimates were calculated using Kaplan-Meier curves SPSS V22.
Results
Out of 33 HCL samples, 21 (63.6%) CRT exon-9 sequencing analyses could be performed and CRT gene mutation was not detected in any. In the clinical analysis of these patients median age was 54 years, with 26 (78.8%) patients were males. Labs at diagnose included median white blood cell was 2.7 x109, Hemoglobin 9.5 g/dL, platelet 58 x109, monocytes 0.28x109, lymphocyte 1.3 x109, neutrophil 1 x109. Laboratory count were found anemia in 22 (%73.3), trombocytopenia in 21 (70%), neutropenia in 14 (48.3%) and monocytopenia in 12 (41.4%) of patients. Out of 33 patients, 27 (90%) had splenomegaly documented at the time of diagnosis. When evaluated pretreatment splenic size by ultrasound, median spleen size was 20.3 centimeter (median %25-75, 16.5-24). Cladribine was used in the treatment of 23 (69.7%) patients. Among these patients’ complete response was 13 (56,5%), partial response was 3 (13%) and overall response was 69.5%. Splenomegaly was significantly high in patients without monocytopenia (p=0.05). There were survival differences between treated (n=23) and untreated (n=10) patient groups (85.6±3 and 17.7±7.8 median months, respectively p=0.001). The patients who treated had significantly longer overall survival compared to those untreated. Furthermore, pretreatment median hemoglobin level was higher in remission group compared to no remission group as 10.1 g/dL vs 8.5 g/dL respectively and there was a statistically significant difference between them (p=0.047).
Conclusion
This is the first study carried out regarding CRT gene mutation in HCL in the literature. We consider that CRT gene mutations are not effective on disease pathogenesis. As a result, spleen size was larger in patients with who had no monocytopenia and initial hemoglobin levels were higher in remission group. This result may be an important finding in terms of timing of treatment in patients with HCL. In this respect, it may be appropriate approach to start to the treatment before anemia develops. Additional larger studies are needed to confirm our results.
Session topic: E-poster
Keyword(s): Anemia, Hairy cell leukemia, Mutation analysis, Spleen
Type: Publication Only
Background
Hairy cell leukemia (HCL) is a malignant hematologic neoplasm characterized by peripheral blood and bone marrow hairy cells. Etiology of disease is not clear. Calreticulin (CRT) is a protein located on endoplasmic reticulum which plays role on protein folding, calcium homeostasis, regulation and loading antigenic peptides into major histocompatibility class-I in the cells. As of today, CRT gene mutations were determined in JAK2 and MPL negative myeloproliferative neoplasms. However, the effect of this gene mutation on hairy cell leukemia which is a lymphoproliferative disease is unknown.
Aims
To study the presence of CRT mutations in hairy cell leukemia and effects.
Methods
A retrospective single institution study chart review of cases with HCL at Gaziantep University between 2005- 2015 was performed. Patients with precise hairy cell leukemia were included. Bone marrow tissue biopsy samples were used. Following the isolation of genetic material and gene sequence analysis by PCR, mutations were investigated for CRT. Complete blood count, peripheral blood smear, bone marrow aspiration and biopsy, flow cytometry were used to diagnose HCL patients. Laboratory counts were determined as anemia <12g/dL, thrombocytopenia <100x109/L, neutropenia <1 x109/L and monocytopenia <0.2 x109/L. We used French Society of Hematology remission criteria for treated hairy cell leukemia. Appropriate ethics approval approval was obtained in accordance with the Helsinki declaration. Comparison between group medians was done using Mann Whitney U, while survival estimates were calculated using Kaplan-Meier curves SPSS V22.
Results
Out of 33 HCL samples, 21 (63.6%) CRT exon-9 sequencing analyses could be performed and CRT gene mutation was not detected in any. In the clinical analysis of these patients median age was 54 years, with 26 (78.8%) patients were males. Labs at diagnose included median white blood cell was 2.7 x109, Hemoglobin 9.5 g/dL, platelet 58 x109, monocytes 0.28x109, lymphocyte 1.3 x109, neutrophil 1 x109. Laboratory count were found anemia in 22 (%73.3), trombocytopenia in 21 (70%), neutropenia in 14 (48.3%) and monocytopenia in 12 (41.4%) of patients. Out of 33 patients, 27 (90%) had splenomegaly documented at the time of diagnosis. When evaluated pretreatment splenic size by ultrasound, median spleen size was 20.3 centimeter (median %25-75, 16.5-24). Cladribine was used in the treatment of 23 (69.7%) patients. Among these patients’ complete response was 13 (56,5%), partial response was 3 (13%) and overall response was 69.5%. Splenomegaly was significantly high in patients without monocytopenia (p=0.05). There were survival differences between treated (n=23) and untreated (n=10) patient groups (85.6±3 and 17.7±7.8 median months, respectively p=0.001). The patients who treated had significantly longer overall survival compared to those untreated. Furthermore, pretreatment median hemoglobin level was higher in remission group compared to no remission group as 10.1 g/dL vs 8.5 g/dL respectively and there was a statistically significant difference between them (p=0.047).
Conclusion
This is the first study carried out regarding CRT gene mutation in HCL in the literature. We consider that CRT gene mutations are not effective on disease pathogenesis. As a result, spleen size was larger in patients with who had no monocytopenia and initial hemoglobin levels were higher in remission group. This result may be an important finding in terms of timing of treatment in patients with HCL. In this respect, it may be appropriate approach to start to the treatment before anemia develops. Additional larger studies are needed to confirm our results.
Session topic: E-poster
Keyword(s): Anemia, Hairy cell leukemia, Mutation analysis, Spleen
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