Informative Value of Combination of Molecular Genetic and Cytogenetic Diagnostic Methods in Myelofibrosis
Journal Title: Lviv Clinical Bulletin - Year 2016, Vol 1, Issue 13
Abstract
Introduction. Myelofibrosis is a rare disease affecting myeloid progenitor stem cells. According to the modern criteria of myelofibrosis diagnostics, the confirmation of the clonality of pathological myeloproliferative process is needed. However, the unique pathognomonic marker for this disease is not revealed. Point missense mutation of JAK2 gene in exon 12 - the JAK2V617F mutation, and karyotype abnormalities are the most frequently found in myelofibrosis patients. In case of additional anomalies the disease prognosis worsens dramatically, in particular, because of higher risk of the transformation to acute leukemia. The purpose of the study was to identify informative combination of molecular genetic and cytogenetic clonal markers for diagnosis and prognosis of myelofibrosis. Materials and research methods. 37 patients were recruited in the study (33 with primary myelofibrosis and 4 with secondary post-polycythemia vera myelofibrosis). Cytogenetic studies were performed for 34 patients. All the patients underwent molecular genetic studies of blood to detect the JAK2V167F mutation. The mutational status of JAK2 gene was reexamined in 10 patients from 1 to 2 years after the initial examination. Results of the investigation and their discussion. The presence of the mutation JAK2V167F was confirmed in 59.5 % of the patients. Chromosomal abnormalities were revealed in 38.2 % of patients. The spectrum of abnormalities included deletions and translocations of chromosome 1, deletions of 5q and 20q, trisomies of chromosomes 3, 8, 9 and 12, monosomies of chromosomes 3, 5, 7, 9, 11, 13, 15 and 17, appearance of іsochromosome 17q, and polyploidy. 4 patients had a complex karyotype. The coincidence of investigated point mutation and karyotype abnormalities was revealed in the total of 8 (21.6 %) patients. The presence of the mutant allele V617F was associated with higher frequency of cytogenetical abnormalities. The complete molecular response to the therapy with hydroxyurea and interferon-α was not achieved in any of the 10 patients who underwent the molecular genetic reexamination. The overall mortality of the patients with JAK2V167F mutation was 27.3 % in 24 months. In the absence of the mutation the mortality rate was slightly lower and constituted 20.0 %. Сytogenetic abnormalities were the only detected clonal markers that allowed to confirm the chronic myeloproliferative process in 13.5 % of patients. Conclusions. Simultaneous cytogenetic analysis and the identification of JAK2V167F mutation increased the rate of clonal confirmation of the pathological process in myelofibrosis patients to 73.0 %, in contrast to 38.2–59.5 % using only one method of investigation. The presence of such cytogenetic anomalies as polyploidy and trisomy of chromosome 9 could result in increase of the copy number of JAK2 gene mutant alleles in pathological cells. The patients having both no detectable level of "wild type" allele of JAK2 gene and considerable quantity of lymphocytes in the blood, could possibly be of higher risk of further transformation of myelofibrosis to acute lymphoid, and not only myeloid leukemia.
Authors and Affiliations
Ростислав Лозинський, М. І. Вороняк, Л. О. Полубень, І. В. Дмитренко, М. Р. Лозинська, Я. І. Виговська, З. В. Масляк
Keywords
Related Articles
- EP ID EP215393
- DOI 10.25040/lkv2016.01.022
- Views 168
- Downloads 0
Ремоделирования левого желудочка у больных стабильной стенокардией, осложненной сердечной недостаточностью, с пониженной и сохраненной фракцией выброса
Введение. Одним из главных компонентов формирования хронической сердечной недостаточности (ХСН), независимо от его этиологии, является ремоделирования сердца. То есть за повреждением миокарда в начале, что приводит к пот...
Високий серцево-судинний ризик населення України: вирок чи точка відліку
Вступ. Серцево-судинні захворювання спричиняють ґлобальні соціально-економічні втрати населення в багатьох країнах світу. В Україні вони на 66,0 % визначають рівень загальної смертності всього населення й на 30,0 % – сме...
Соматотипологическая характеристика больных ревматоидным артритом в зависимости от возраста пациентов, возраста, в котором началось заболевание и его продолжительности
Введение. Ревматоидный артрит (РА) - мультифакториальное аутоиммунное заболевание, на возникновение которого влияет множество факторов, прежде всего генетических, эндокринных и средовых (социально-экономических). Перспек...
Pneumonia in Children: Pharmacogenetic Aspect in the Appearence of the Severe Forms and Complications of the Disease (Literature Review and Clinical Case Presentation)
Introduction. Respiratory system diseases were and continue to be a topical problem of the medicine overall and pediatrics in particular. Pneumonia is the most serious disease that kills children under 5 years old global...
Оптимізація діаґностично-лікувальної тактики стосовно ретенованих нижніх третіх молярів із використанням авторської програми комп’ютерного моделювання
Вступ. Значний відсоток внутрішньо- і післяопераційних ускладнень змусив шукати нові засади діаґностики, вибору методики операції атипового видалення нижніх третіх молярів, проґнозування перебігу операції та післяопераці...