EHA Library - The official digital education library of European Hematology Association (EHA)

COMPREHENSIVE STUDY OF BCR/ABL GENE EXPRESSION IN PROGRESSION OF “CLASSIC” MYELOPROLIFERATIVE DISORDERS
Author(s):
Laura Kesaeva
,
Laura Kesaeva
Affiliations:
N.N.Blokhin Russian Cancer Research Center,GeneTechnology LLC,Moscow,Russian Federation
Andrey Misyurin
,
Andrey Misyurin
Affiliations:
.N.Blokhin Russian Cancer Research Center,GeneTechnology LLC,Moscow,Russian Federation
Vera Tikhonova
,
Vera Tikhonova
Affiliations:
N.N.Blokhin Russian Cancer Research Center,GeneTechnology LLC,Moscow,Russian Federation
Yulia Finashutina
,
Yulia Finashutina
Affiliations:
.N.Blokhin Russian Cancer Research Center,GeneTechnology LLC,Moscow,Russian Federation
Hasmik Mkrtchyan
,
Hasmik Mkrtchyan
Affiliations:
GeneTechnology LLC,Moscow,Russian Federation
Vsevolod Misyurin
,
Vsevolod Misyurin
Affiliations:
Kashirskoe shosse, 24,GeneTechnology LLC,Moscow,Russian Federation
Natalya Kasatkina
,
Natalya Kasatkina
Affiliations:
N.N.Blokhin Russian Cancer Research Center,Moscow,Russian Federation
Aleksey Krutov
,
Aleksey Krutov
Affiliations:
GeneTechnology LLC,Moscow,Russian Federation
Irina Soldatova
,
Irina Soldatova
Affiliations:
GeneTechnology LLC,Moscow,Russian Federation
Elena Misyurina
Elena Misyurina
Affiliations:
GeneTechnology LLC,Moscow,Russian Federation
(Abstract release date: 05/18/17) EHA Library. Kesaeva L. 05/18/17; 182740; PB2026
Ms. Laura Kesaeva
Ms. Laura Kesaeva
Contributions
PDF Abstract
Abstract

Abstract: PB2026

Type: Publication Only

Background

Classic myeloproliferative disorders (MPDs) also known as chronical MPDs, include several clonal hematologic diseases (such as polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF)), which are negative for t(9;22) translocation, result to BCR/ABL chimeric gene expression . Characterization of JAK2V617F mutation, deletion in 12 exon of JAK2 gene, MPL W515L/K, mutation in calreticulin gene (CALR) contributed a lot to understanding of molecular pathogenesis of MPDs. However, detailed molecular mechanism underlying the progression of MPD remains unclear. Several cases of MPDs with detected BCR/ABL expression were described repeatedly in previons publications. The phenomen of simultaneous coincidence of mentioned molecular markers in each clinical case requires comprehensive study.

Aims

The aim our work was to investigate BCR/ABL expression in therapy resistant MPD patients with disease progression.

Methods

Peripheral blood samples 175 patients with progressive MPD and 67 patients with primary MPD was used as a biological material for experiments. Qualitative and quantitative analysis of BCR/ABL gene (р190, р210, р230) was performed by two-step PCR and real-time PCR. Jak2, Jak2-e12, MPL, CALR mutations were determined by direct sequencing and allele-specific PCR. RAG1 and RAG2 expression was analyzed by real-time PCR.

Results
175 patients with progressive MPD were analysed: 35(20%)- PV, 38(22%)- ET, 102(58%)-PMF. BCR/ABL gene expression was identified in 47 cases (32,83%). We found 44 cases with BCR/Abl /р210, 3 cases with BCR/Abl/р190, and no cases of BCR/Abl/р230. We have observed hepatomegaly (17/43- 40%) and elevated WBC in BCR/ABL positive cases. JAK2V617F mutation was identified in 139 patients, deletion in 12 exon of JAK2 gene was found in 2 patients. One case with MPL W515L mutation and 11 cases with CALR mutation were identified. Group of primary MPD patients (N= 67)- 26(47%)-PV, 21(38%)-ET, 8(15%)-PMF, contained 55/67(82%) patients with JAK2V617F mutation. Expression of BCR/ABL/р210 was detected only in 2/55(3,6%). We also found that expression levels of key components of V(D)J recombinase RAG1 and RAG2 in granulocytes is higher in Jak 2V617F-positive MPDs patients(46/49- 94% cases) compared to heathy donors (3/42- 7%).

Conclusion

The normal rearrangement of immunoglobulin receptors in maturing B-lymphocytes depends on JAK-kinases activation. Therefore we suppose that activation of key components of V(D)J recombinase (RAG1/RAG2) could lead to appearance of additional clone with chimeric BCR/ABL due to increased tension of Jak-STAT pathway.. The expression of BCR/ABL gene could be the possible reason for MPD progression and should be considered as an indication for complementary therapy.

Session topic: 15. Myeloproliferative neoplasms - Biology

Abstract: PB2026

Type: Publication Only

Background

Classic myeloproliferative disorders (MPDs) also known as chronical MPDs, include several clonal hematologic diseases (such as polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF)), which are negative for t(9;22) translocation, result to BCR/ABL chimeric gene expression . Characterization of JAK2V617F mutation, deletion in 12 exon of JAK2 gene, MPL W515L/K, mutation in calreticulin gene (CALR) contributed a lot to understanding of molecular pathogenesis of MPDs. However, detailed molecular mechanism underlying the progression of MPD remains unclear. Several cases of MPDs with detected BCR/ABL expression were described repeatedly in previons publications. The phenomen of simultaneous coincidence of mentioned molecular markers in each clinical case requires comprehensive study.

Aims

The aim our work was to investigate BCR/ABL expression in therapy resistant MPD patients with disease progression.

Methods

Peripheral blood samples 175 patients with progressive MPD and 67 patients with primary MPD was used as a biological material for experiments. Qualitative and quantitative analysis of BCR/ABL gene (р190, р210, р230) was performed by two-step PCR and real-time PCR. Jak2, Jak2-e12, MPL, CALR mutations were determined by direct sequencing and allele-specific PCR. RAG1 and RAG2 expression was analyzed by real-time PCR.

Results
175 patients with progressive MPD were analysed: 35(20%)- PV, 38(22%)- ET, 102(58%)-PMF. BCR/ABL gene expression was identified in 47 cases (32,83%). We found 44 cases with BCR/Abl /р210, 3 cases with BCR/Abl/р190, and no cases of BCR/Abl/р230. We have observed hepatomegaly (17/43- 40%) and elevated WBC in BCR/ABL positive cases. JAK2V617F mutation was identified in 139 patients, deletion in 12 exon of JAK2 gene was found in 2 patients. One case with MPL W515L mutation and 11 cases with CALR mutation were identified. Group of primary MPD patients (N= 67)- 26(47%)-PV, 21(38%)-ET, 8(15%)-PMF, contained 55/67(82%) patients with JAK2V617F mutation. Expression of BCR/ABL/р210 was detected only in 2/55(3,6%). We also found that expression levels of key components of V(D)J recombinase RAG1 and RAG2 in granulocytes is higher in Jak 2V617F-positive MPDs patients(46/49- 94% cases) compared to heathy donors (3/42- 7%).

Conclusion

The normal rearrangement of immunoglobulin receptors in maturing B-lymphocytes depends on JAK-kinases activation. Therefore we suppose that activation of key components of V(D)J recombinase (RAG1/RAG2) could lead to appearance of additional clone with chimeric BCR/ABL due to increased tension of Jak-STAT pathway.. The expression of BCR/ABL gene could be the possible reason for MPD progression and should be considered as an indication for complementary therapy.

Session topic: 15. Myeloproliferative neoplasms - Biology

Premium Sponsors

What's new at EHA

Browse the open-source material from EHA past Congresses and meetings.

References

EHA Terms & Conditions
2025 ©
European Hematology Association
USER TERMS AND CONDITIONS / PRIVACY POLICY
(Amended according to GDPR)

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies