OncohematologyOncohematologyОнкогематология1818-83462413-4023Publishing House ABV Press7710.17650/1818-8346-2011-6-4-6-11HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CAREГЕМОБЛАСТОЗЫ: ДИАГНОСТИКА, ЛЕЧЕНИЕ, СОПРОВОДИТЕЛЬНАЯ ТЕРАПИЯFamily platelet disorder with propensity to acute myeloid leukemia: new family with RUNX1 mutationСемейная тромбоцитопения/тромбоцитопатия с предрасположенностью к развитию острого миелоидного лейкоза: описание новой семьи и мутации в гене RUNX1BobryninaV. O.БобрынинаВ. О.
Russian Federation
vlastabobrynina@yandex.ruBaranovaO. Yu.БарановаО. Ю.
Russian Federation
Samochatova1,E. V.СамочатоваЕ. В.
Russian Federation
MaschanA. A.МасчанА. А.
Russian Federation
Federal Research Center of Pediatric Hematology, Oncology and ImmunologyФГБУ Федеральный научно-клинический центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева Минздравсоцразвития РоссииN.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical SciencesФГБУ Российский онкологический научный центр им. Н.Н. Блохина РАМН231120116461123072014230720142011https://oncohematology.abvpress.ru/ongm/article/view/77

Familial platelet disorder with propensity to develop acute myeloid leukemia (FPD/AML) is a rare autosomal dominant disorder caused by inherited mutation of RUNX1. To date only 35 families have been described. We report on a family in which number and function of platelet were impaired in members of 4 generations. Acute myeloid leukemia developed in 3 members of 2 generations. The age of leukemia development was 11, 19 и 76 years. In all 5 affected family members available for study novel heterozygous mutation in runt domain of RUNX1 (c2018 A > C, pT147P) was detected by direct sequencing. This mutation is predicted to impair binding of CBF to core motif of DNA. Two affected patients died of leukemia; while in one complete remission was achieved with conventional and consolidated with allogeneic BMT from HLA-matched sister proved to be RUNX1 mutation negative.

Семейная тромбоцитопения/тромбоцитопатия с предрасположенностью к развитию острого миелоидного лейкоза (ОМЛ) является редким аутосомно-доминантным синдромом, связанным с мутацией в гене RUNX1. К настоящему времени известно 35 семей с данным заболеванием. Мы описываем семью, в которой у 6 членов в 4 поколениях зарегистрировано нарушение функции и числа тромбоцитов и у 3 членов в 2 поколениях развился ОМЛ. Возраст развития ОМЛ составил 11, 19 и 76 лет. При молекулярно-биологическом анализе у 5 доступных для исследования членов семьи выявлена новая мутация гена RUNX1 (c.2018 A > C, p.T147P), локализующаяся в Runt-домене. Описанная мутация должна нарушать связь транскрипционного комплекса CBF c ДНК. Два пациента с ОМЛ умерли и у 1 проведена успешная трансплантация гемопоэтических клеток от HLA-идентичного сиблинга, у которого было доказано отсутствие мутации в гене RUNX1.

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