WHAT IS THE SECRET OF THE JAK2 MUTATION ALLELE LOAD STABILITY IN SOME PATIENTS WITH MPN?
(Abstract release date: 05/19/16)
EHA Library. Subbotina T. 06/09/16; 134938; PB2038
Dr. Tatiana Subbotina
Contributions
Contributions
Abstract
Abstract: PB2038
Type: Publication Only
Background
It is known that the level of JAK2 mutation allele load in patients with myeloproliferative neoplasms (MPN) in the disease dynamics can be continuously stable and not be associated with clinical symptoms or effects of hydroxyurea (HU) (Theocharides A et al, Haematologica, 2008; Besses C et al, Br J Haematol, 2011). Reasons and mechanisms of this kind of «homeostasis» in the level of circulating mutation JAK2 positive cells in some patients are unclear.
Aims
Evaluate the level of JAK2 mutation allele load in MPN patients in the disease dynamics and HU effects.
Methods
This study included 14 JAK2 positive (V617F or exon 12 mutations) MPN patients. The informed consents from these patients were obtained. DNA was extracted from venous blood leukocytes. Quantification of JAK2 V617F and JAK2 exon 12 mutations allele load was performed by pyrosequencing method as described in (Dunaeva E et al Klin Lab Diagn, 2014). JAK2 variance (MUT) was calculated as a measure of relative changes in allele load between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Following variants were identified according to the level of JAK2 mutation allele load in the disease dynamics and HU effects (Table 1): 1) The level of JAK2 mutation allele load was increased more than twice (№3 and №13). Until now this patients do not have the significant clinical MPN manifestations and do not need HU-treatment; 2) The level of JAK2 mutation allele load was found to remain stable over follow-up time of observation independently of whether patients were already or not under HU treatment at the time of first sampling; 3) The level of JAK2 mutation allele load was reduced after HU treatment. We did not find any dependency between the allele load dynamics and patient's clinical status, disease phenotype, disease duration and venous blood cellular account.Table 1. Characteristics of the patients included in the study.
* – The allelic load was determined at the primary address to the doctor with MPN symptoms
Conclusion
Our data suggest the JAK2 mutation allele load can remain stable for a long time in some patients. The observed increase of the mutation allele load in untreated patients probably will be to increase to the level of its stabilization at full development of the clinical MPN picture. The differences of the allele load dynamics between individual patients may be associated with the individual features of the intracellular signaling networks and will be the subject of additional studies.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder
Type: Publication Only
Background
It is known that the level of JAK2 mutation allele load in patients with myeloproliferative neoplasms (MPN) in the disease dynamics can be continuously stable and not be associated with clinical symptoms or effects of hydroxyurea (HU) (Theocharides A et al, Haematologica, 2008; Besses C et al, Br J Haematol, 2011). Reasons and mechanisms of this kind of «homeostasis» in the level of circulating mutation JAK2 positive cells in some patients are unclear.
Aims
Evaluate the level of JAK2 mutation allele load in MPN patients in the disease dynamics and HU effects.
Methods
This study included 14 JAK2 positive (V617F or exon 12 mutations) MPN patients. The informed consents from these patients were obtained. DNA was extracted from venous blood leukocytes. Quantification of JAK2 V617F and JAK2 exon 12 mutations allele load was performed by pyrosequencing method as described in (Dunaeva E et al Klin Lab Diagn, 2014). JAK2 variance (MUT) was calculated as a measure of relative changes in allele load between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Following variants were identified according to the level of JAK2 mutation allele load in the disease dynamics and HU effects (Table 1): 1) The level of JAK2 mutation allele load was increased more than twice (№3 and №13). Until now this patients do not have the significant clinical MPN manifestations and do not need HU-treatment; 2) The level of JAK2 mutation allele load was found to remain stable over follow-up time of observation independently of whether patients were already or not under HU treatment at the time of first sampling; 3) The level of JAK2 mutation allele load was reduced after HU treatment. We did not find any dependency between the allele load dynamics and patient's clinical status, disease phenotype, disease duration and venous blood cellular account.Table 1. Characteristics of the patients included in the study.
| № | Age of manifestation (years) | Sex | Disease | HU | % JAK2 mutation baseline | % JAK2 mutation last sample | JAK2 variance (MUT) | Time between two assessments (mo) |
| JAK2 V617F mutation-positive patients | ||||||||
| 1 | 67 | F | ET* | No | 29 | 27 | n.s. | 6 |
| 2 | 70 | F | PV | No | 34 | 32 | n.s. | 10 |
| 3 | 71 | F | PV | No | 16 | 35 | +115 | 18 |
| 4 | 59 | F | Post-PV MF | Yes | 82 | 86 | n.s. | 15 |
| 5 | 51 | F | PV | Yes | 78 | 73 | n.s. | 20 |
| 6 | 44 | F | PV | Yes | 69 | 77 | +11 | 12 |
| 7 | 59 | F | PV* | Yes | 42 | 42 | n.s. | 27 |
| 8 | 45 | F | ET* | Yes | 8 | 7 | n.s. | 36 |
| 9 | 75 | F | Post-ET MF* | Yes | 14 | 10 | -38 | 18 |
| 10 | 57 | F | PV* | Yes | 31 | 22 | -29 | 6 |
| 11 | 59 | F | PV | Yes | 81 | 54 | -33 | 36 |
| 12 | 35 | M | MF | Yes | 27 | 20 | -27 | 15 |
| JAK2 exon 12 mutation-positive patients | ||||||||
| 13 | 61 | M | PV* | No | 15 | 40 | +166 | 24 |
| 14 | 48 | M | PV* | No | 11 | 11 | n.s. | 4 |
Conclusion
Our data suggest the JAK2 mutation allele load can remain stable for a long time in some patients. The observed increase of the mutation allele load in untreated patients probably will be to increase to the level of its stabilization at full development of the clinical MPN picture. The differences of the allele load dynamics between individual patients may be associated with the individual features of the intracellular signaling networks and will be the subject of additional studies.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder
Abstract: PB2038
Type: Publication Only
Background
It is known that the level of JAK2 mutation allele load in patients with myeloproliferative neoplasms (MPN) in the disease dynamics can be continuously stable and not be associated with clinical symptoms or effects of hydroxyurea (HU) (Theocharides A et al, Haematologica, 2008; Besses C et al, Br J Haematol, 2011). Reasons and mechanisms of this kind of «homeostasis» in the level of circulating mutation JAK2 positive cells in some patients are unclear.
Aims
Evaluate the level of JAK2 mutation allele load in MPN patients in the disease dynamics and HU effects.
Methods
This study included 14 JAK2 positive (V617F or exon 12 mutations) MPN patients. The informed consents from these patients were obtained. DNA was extracted from venous blood leukocytes. Quantification of JAK2 V617F and JAK2 exon 12 mutations allele load was performed by pyrosequencing method as described in (Dunaeva E et al Klin Lab Diagn, 2014). JAK2 variance (MUT) was calculated as a measure of relative changes in allele load between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Following variants were identified according to the level of JAK2 mutation allele load in the disease dynamics and HU effects (Table 1): 1) The level of JAK2 mutation allele load was increased more than twice (№3 and №13). Until now this patients do not have the significant clinical MPN manifestations and do not need HU-treatment; 2) The level of JAK2 mutation allele load was found to remain stable over follow-up time of observation independently of whether patients were already or not under HU treatment at the time of first sampling; 3) The level of JAK2 mutation allele load was reduced after HU treatment. We did not find any dependency between the allele load dynamics and patient's clinical status, disease phenotype, disease duration and venous blood cellular account.Table 1. Characteristics of the patients included in the study.
* – The allelic load was determined at the primary address to the doctor with MPN symptoms
Conclusion
Our data suggest the JAK2 mutation allele load can remain stable for a long time in some patients. The observed increase of the mutation allele load in untreated patients probably will be to increase to the level of its stabilization at full development of the clinical MPN picture. The differences of the allele load dynamics between individual patients may be associated with the individual features of the intracellular signaling networks and will be the subject of additional studies.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder
Type: Publication Only
Background
It is known that the level of JAK2 mutation allele load in patients with myeloproliferative neoplasms (MPN) in the disease dynamics can be continuously stable and not be associated with clinical symptoms or effects of hydroxyurea (HU) (Theocharides A et al, Haematologica, 2008; Besses C et al, Br J Haematol, 2011). Reasons and mechanisms of this kind of «homeostasis» in the level of circulating mutation JAK2 positive cells in some patients are unclear.
Aims
Evaluate the level of JAK2 mutation allele load in MPN patients in the disease dynamics and HU effects.
Methods
This study included 14 JAK2 positive (V617F or exon 12 mutations) MPN patients. The informed consents from these patients were obtained. DNA was extracted from venous blood leukocytes. Quantification of JAK2 V617F and JAK2 exon 12 mutations allele load was performed by pyrosequencing method as described in (Dunaeva E et al Klin Lab Diagn, 2014). JAK2 variance (MUT) was calculated as a measure of relative changes in allele load between the baseline and follow-up sample (Theocharides A et al, Haematologica, 2008).
Results
Following variants were identified according to the level of JAK2 mutation allele load in the disease dynamics and HU effects (Table 1): 1) The level of JAK2 mutation allele load was increased more than twice (№3 and №13). Until now this patients do not have the significant clinical MPN manifestations and do not need HU-treatment; 2) The level of JAK2 mutation allele load was found to remain stable over follow-up time of observation independently of whether patients were already or not under HU treatment at the time of first sampling; 3) The level of JAK2 mutation allele load was reduced after HU treatment. We did not find any dependency between the allele load dynamics and patient's clinical status, disease phenotype, disease duration and venous blood cellular account.Table 1. Characteristics of the patients included in the study.
| № | Age of manifestation (years) | Sex | Disease | HU | % JAK2 mutation baseline | % JAK2 mutation last sample | JAK2 variance (MUT) | Time between two assessments (mo) |
| JAK2 V617F mutation-positive patients | ||||||||
| 1 | 67 | F | ET* | No | 29 | 27 | n.s. | 6 |
| 2 | 70 | F | PV | No | 34 | 32 | n.s. | 10 |
| 3 | 71 | F | PV | No | 16 | 35 | +115 | 18 |
| 4 | 59 | F | Post-PV MF | Yes | 82 | 86 | n.s. | 15 |
| 5 | 51 | F | PV | Yes | 78 | 73 | n.s. | 20 |
| 6 | 44 | F | PV | Yes | 69 | 77 | +11 | 12 |
| 7 | 59 | F | PV* | Yes | 42 | 42 | n.s. | 27 |
| 8 | 45 | F | ET* | Yes | 8 | 7 | n.s. | 36 |
| 9 | 75 | F | Post-ET MF* | Yes | 14 | 10 | -38 | 18 |
| 10 | 57 | F | PV* | Yes | 31 | 22 | -29 | 6 |
| 11 | 59 | F | PV | Yes | 81 | 54 | -33 | 36 |
| 12 | 35 | M | MF | Yes | 27 | 20 | -27 | 15 |
| JAK2 exon 12 mutation-positive patients | ||||||||
| 13 | 61 | M | PV* | No | 15 | 40 | +166 | 24 |
| 14 | 48 | M | PV* | No | 11 | 11 | n.s. | 4 |
Conclusion
Our data suggest the JAK2 mutation allele load can remain stable for a long time in some patients. The observed increase of the mutation allele load in untreated patients probably will be to increase to the level of its stabilization at full development of the clinical MPN picture. The differences of the allele load dynamics between individual patients may be associated with the individual features of the intracellular signaling networks and will be the subject of additional studies.
Session topic: E-poster
Keyword(s): Myeloproliferative disorder
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