Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD
JAK2-V617F mutation in patients with myeloproliferative neoplasms: Association with FLT3-ITD mutation
Apstrakt
Uvod. Stečena somatska mutacija V617F u genu za Janus kinazu 2 (JAK2) uzrok je nekontrolisane proliferacije ćelija kod bolesnika s mijeloproliferativnim neoplazijama. Poznato je da do proliferacije ćelija mijeloidne loze dolazi i pod uticajem mutacija u drugim genima, kao što su mutacije u genu za tirozin-kinazni receptor FLT3, koji je najčešći mutirani gen u akutnim mijeloidnim leukemijama. Od posebnog je značaja to što mutirani protein FLT3 koristi isti signalni put kao protein JAK2. To je signalni put preko proteina STAT5, čija je aktivacija važna za samoobnavljanje matičnih ćelija hematopoeze. Cilj rada. Cilj istraživanja je bio da se otkrije mutacija V617F u genu za JAK2 kod bolesnika s mijeloproliferativnim neoplazijama. Ispitano je i istovremeno prisustvo mutacije FLT3-ITD kod ovih bolesnika radi rasvetljavanja hipoteze o sličnoj ulozi ova dva molekularnogenetička markera u hematološkim malignitetima. Metode rada. Metodom alel-specifičnog PCR (engl. polymerase chain reaction) an...aliziran je 61 bolesnik sa potvrđenom dijagnozom mijeloproliferativne neoplazije na mutaciju V617F u genu za JAK2 ili sumnjom na ovu dijagnozu. Kod bolesnika sa mutacijom u genu JAK2 je zatim ispitano postojanje mutacije FLT3-ITD metodom PCR. Rezultati. Kod 18 ispitanika je otkrivena mutacija V617F u genu za JAK2. Među njima je kod osam bolesnika dijagnostikovana policitemija vera, a kod deset esencijalna trombocitemija. Ni kod jednog ispitanika s mutacijom V617F u genu za JAK2 nije otkrivena mutacija FLT3-ITD. Zaključak. Rezultati ovog istraživanja podržavaju hipotezu da je za malignu transformaciju matične ćelije hematopoeze dovoljna jedna mutacija koja izaziva poremećaj proliferacije ćelije.
Introduction. An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is the cause of uncontrolled proliferation in patients with myeloproliferative neoplasms. It is known that uncontrolled myeloid cell proliferation is also provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid leukaemia. Interestingly, mutated FLT3- ITD (internal tandem duplication) protein is a member of the same signalling pathway as JAK2 protein, the STAT5 signalling pathway. STAT5 activation is recognized as important for selfrenewal of haematopoetic stem cells. Objective. The aim of this study was the detection of JAK2- V617F mutation in patients with myeloproliferative neoplasms. Additionally, we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients in order to shed the light on the hypothesis of a similar role of these two molecular markers in haematological malignancies. Me...thods. Using allele-specific PCR, 61 patients with known or suspected diagnosis of myeloproliferative neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD mutation by PCR. Results. Eighteen of 61 analysed patients were positive for JAK2-V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera, and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was positive for FLT3-ITD mutation. Conclusion. This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell.
Ključne reči:
mutacija JAK2-V617F / mutacija FLT3-ITD / mijeloproliferativne neoplazije / alel-specifični PCR / myeloproliferative neoplasms / JAK2-V617F mutation / FLT3-ITD mutation / allele-specific PCRIzvor:
Srpski arhiv za celokupno lekarstvo, 2010, 138, 9-10, 614-618Izdavač:
- Srpsko lekarsko društvo, Beograd
Finansiranje / projekti:
- Molekularno genetski markeri klonskog preobražaja matičnih ćelija hematopoeze (RS-MESTD-MPN2006-2010-145061)
DOI: 10.2298/SARH1010614S
ISSN: 0370-8179
PubMed: 21180092
WoS: 000209955600013
Scopus: 2-s2.0-79951594448
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Spasovski, Vesna AU - Tošić, Nataša AU - Kostić, Tatjana AU - Pavlović, Sonja AU - Čolović, Milica PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/470 AB - Uvod. Stečena somatska mutacija V617F u genu za Janus kinazu 2 (JAK2) uzrok je nekontrolisane proliferacije ćelija kod bolesnika s mijeloproliferativnim neoplazijama. Poznato je da do proliferacije ćelija mijeloidne loze dolazi i pod uticajem mutacija u drugim genima, kao što su mutacije u genu za tirozin-kinazni receptor FLT3, koji je najčešći mutirani gen u akutnim mijeloidnim leukemijama. Od posebnog je značaja to što mutirani protein FLT3 koristi isti signalni put kao protein JAK2. To je signalni put preko proteina STAT5, čija je aktivacija važna za samoobnavljanje matičnih ćelija hematopoeze. Cilj rada. Cilj istraživanja je bio da se otkrije mutacija V617F u genu za JAK2 kod bolesnika s mijeloproliferativnim neoplazijama. Ispitano je i istovremeno prisustvo mutacije FLT3-ITD kod ovih bolesnika radi rasvetljavanja hipoteze o sličnoj ulozi ova dva molekularnogenetička markera u hematološkim malignitetima. Metode rada. Metodom alel-specifičnog PCR (engl. polymerase chain reaction) analiziran je 61 bolesnik sa potvrđenom dijagnozom mijeloproliferativne neoplazije na mutaciju V617F u genu za JAK2 ili sumnjom na ovu dijagnozu. Kod bolesnika sa mutacijom u genu JAK2 je zatim ispitano postojanje mutacije FLT3-ITD metodom PCR. Rezultati. Kod 18 ispitanika je otkrivena mutacija V617F u genu za JAK2. Među njima je kod osam bolesnika dijagnostikovana policitemija vera, a kod deset esencijalna trombocitemija. Ni kod jednog ispitanika s mutacijom V617F u genu za JAK2 nije otkrivena mutacija FLT3-ITD. Zaključak. Rezultati ovog istraživanja podržavaju hipotezu da je za malignu transformaciju matične ćelije hematopoeze dovoljna jedna mutacija koja izaziva poremećaj proliferacije ćelije. AB - Introduction. An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is the cause of uncontrolled proliferation in patients with myeloproliferative neoplasms. It is known that uncontrolled myeloid cell proliferation is also provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid leukaemia. Interestingly, mutated FLT3- ITD (internal tandem duplication) protein is a member of the same signalling pathway as JAK2 protein, the STAT5 signalling pathway. STAT5 activation is recognized as important for selfrenewal of haematopoetic stem cells. Objective. The aim of this study was the detection of JAK2- V617F mutation in patients with myeloproliferative neoplasms. Additionally, we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients in order to shed the light on the hypothesis of a similar role of these two molecular markers in haematological malignancies. Methods. Using allele-specific PCR, 61 patients with known or suspected diagnosis of myeloproliferative neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD mutation by PCR. Results. Eighteen of 61 analysed patients were positive for JAK2-V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera, and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was positive for FLT3-ITD mutation. Conclusion. This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell. PB - Srpsko lekarsko društvo, Beograd T2 - Srpski arhiv za celokupno lekarstvo T1 - Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD T1 - JAK2-V617F mutation in patients with myeloproliferative neoplasms: Association with FLT3-ITD mutation EP - 618 IS - 9-10 SP - 614 VL - 138 DO - 10.2298/SARH1010614S ER -
@article{ author = "Spasovski, Vesna and Tošić, Nataša and Kostić, Tatjana and Pavlović, Sonja and Čolović, Milica", year = "2010", abstract = "Uvod. Stečena somatska mutacija V617F u genu za Janus kinazu 2 (JAK2) uzrok je nekontrolisane proliferacije ćelija kod bolesnika s mijeloproliferativnim neoplazijama. Poznato je da do proliferacije ćelija mijeloidne loze dolazi i pod uticajem mutacija u drugim genima, kao što su mutacije u genu za tirozin-kinazni receptor FLT3, koji je najčešći mutirani gen u akutnim mijeloidnim leukemijama. Od posebnog je značaja to što mutirani protein FLT3 koristi isti signalni put kao protein JAK2. To je signalni put preko proteina STAT5, čija je aktivacija važna za samoobnavljanje matičnih ćelija hematopoeze. Cilj rada. Cilj istraživanja je bio da se otkrije mutacija V617F u genu za JAK2 kod bolesnika s mijeloproliferativnim neoplazijama. Ispitano je i istovremeno prisustvo mutacije FLT3-ITD kod ovih bolesnika radi rasvetljavanja hipoteze o sličnoj ulozi ova dva molekularnogenetička markera u hematološkim malignitetima. Metode rada. Metodom alel-specifičnog PCR (engl. polymerase chain reaction) analiziran je 61 bolesnik sa potvrđenom dijagnozom mijeloproliferativne neoplazije na mutaciju V617F u genu za JAK2 ili sumnjom na ovu dijagnozu. Kod bolesnika sa mutacijom u genu JAK2 je zatim ispitano postojanje mutacije FLT3-ITD metodom PCR. Rezultati. Kod 18 ispitanika je otkrivena mutacija V617F u genu za JAK2. Među njima je kod osam bolesnika dijagnostikovana policitemija vera, a kod deset esencijalna trombocitemija. Ni kod jednog ispitanika s mutacijom V617F u genu za JAK2 nije otkrivena mutacija FLT3-ITD. Zaključak. Rezultati ovog istraživanja podržavaju hipotezu da je za malignu transformaciju matične ćelije hematopoeze dovoljna jedna mutacija koja izaziva poremećaj proliferacije ćelije., Introduction. An acquired somatic mutation V617F in Janus kinase 2 gene (JAK2) is the cause of uncontrolled proliferation in patients with myeloproliferative neoplasms. It is known that uncontrolled myeloid cell proliferation is also provoked by alteration in other genes, e.g. mutations in receptor tyrosine kinase FLT3 gene. FLT3 represents the most frequently mutated gene in acute myeloid leukaemia. Interestingly, mutated FLT3- ITD (internal tandem duplication) protein is a member of the same signalling pathway as JAK2 protein, the STAT5 signalling pathway. STAT5 activation is recognized as important for selfrenewal of haematopoetic stem cells. Objective. The aim of this study was the detection of JAK2- V617F mutation in patients with myeloproliferative neoplasms. Additionally, we investigated the presence of FLT3-ITD mutation in JAK2-V617F-positive patients in order to shed the light on the hypothesis of a similar role of these two molecular markers in haematological malignancies. Methods. Using allele-specific PCR, 61 patients with known or suspected diagnosis of myeloproliferative neoplasms were tested for the presence of JAK2-V617F mutation. Samples that were positive for JAK2 mutation were subsequently tested for the presence of FLT3-ITD mutation by PCR. Results. Eighteen of 61 analysed patients were positive for JAK2-V617F mutation. Among them, 8/18 samples were diagnosed as polycythaemia vera, and 10/18 as essential thrombocythaemia. None of JAK2-V617F-positive patient was positive for FLT3-ITD mutation. Conclusion. This study suggests that one activating mutation is sufficient for aberrant cell proliferation leading to malignant transformation of haematopoetic stem cell.", publisher = "Srpsko lekarsko društvo, Beograd", journal = "Srpski arhiv za celokupno lekarstvo", title = "Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD, JAK2-V617F mutation in patients with myeloproliferative neoplasms: Association with FLT3-ITD mutation", pages = "618-614", number = "9-10", volume = "138", doi = "10.2298/SARH1010614S" }
Spasovski, V., Tošić, N., Kostić, T., Pavlović, S.,& Čolović, M.. (2010). Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD. in Srpski arhiv za celokupno lekarstvo Srpsko lekarsko društvo, Beograd., 138(9-10), 614-618. https://doi.org/10.2298/SARH1010614S
Spasovski V, Tošić N, Kostić T, Pavlović S, Čolović M. Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD. in Srpski arhiv za celokupno lekarstvo. 2010;138(9-10):614-618. doi:10.2298/SARH1010614S .
Spasovski, Vesna, Tošić, Nataša, Kostić, Tatjana, Pavlović, Sonja, Čolović, Milica, "Mutacija JAK2-V617F kod bolesnika s mijeloproliferativnim neoplazijama - veza sa mutacijom FLT3-ITD" in Srpski arhiv za celokupno lekarstvo, 138, no. 9-10 (2010):614-618, https://doi.org/10.2298/SARH1010614S . .