Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

The Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2) on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4%) who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%)

Ring chromosome 18 abnormality in acute myelogenous leukemia: the clinical dilemma

The ring chromosome is a circular, structural abnormality composed of either multiple chromosomes or a single chromosome with loss of genetic material at one or both ends. This chromosomal rearrangement is often unstable with frequent recombinations and may be accompanied by either loss or amplification of genetic material[1]. Considering that ring chromosomes are rare in acute myelogenous leukemia (AML), it is difficult to risk stratify patient prognosis, particularly when the ring chromosome occurs as the sole abnormality. Here we report a case of a ring chromosome 18 abnormality in a patient with newly diagnosed AML with monocytic differentiation. Cytogenetic analysis demonstrated 46, XY, r(18)(p11q21) karyotype in 19 of 34 evaluated metaphase cells. The patient received induction chemotherapy and subsequent allogeneic cord blood transplant from a sex-matched donor, and remained in hematologic and cytogenetic remission for 120 days post transplant. Soon after, he developed post transplant lymphoproliferative disorder and died of multi-organ failure. Although r(18) chromosomal abnormalities were not classified in the recent updated evidence-and expert opinion-based recommendations for the diagnosis and management of AML (likely due to the small number of reported cases), the patient was treated as high risk with stem cell transplantation. This was based on the unstable nature of the ring chromosome and the poor outcomes described in the literature of patients with sole ring 18 abnormalities

Development of Myelodysplastic Syndrome and Acute Myeloid Leukemia 15 Years after Hydroxyurea Use in a Patient with Sickle Cell Anemia

We report a 41 year old male with sickle cell disease who developed a myelodysplastic syndrome and acute myeloid leukemia with complex karyotype involving chromosomes 5, 7 and 17 after 15 years of hydroxyurea treatment. He responded poorly to induction chemotherapy with cytarabine/idarubicin followed by high dose cytarabine and succumbed to neutropenic sepsis. Multiple systematic reviews, observational studies and clinical trials were conducted to identify the toxicity profile of hydroxurea. Only six cases of leukemia/myelodysplastic syndrome were identified in patients with sickle cell anemia treated with hydroxyurea. Subsequently, it was concluded that hydroxyurea is not leukemogenic. However, it was noted that most of the published studies had only up to 9 years of follow-up. Our patient was started on hydroxyurea in 1990, before the widespread use of the drug and took hydroxyurea for 15 years. His presentation may reflect an outcome otherwise not yet observed because of the short follow-up of prior studies. We believe that the leukemogenic risk of hydroxyurea should be discussed with the patients and their families. Studies evaluating the adverse effects of hydroxyurea should have longer follow-up before definitive conclusions are drawn

Dr Alfred Najfeld - sećanje na razgovore sa našim ocem

In five books, "We Survived: Yugoslav Jews on the Holocaust" (three of them translated into English), the testimonies of a small number of surviving members of the Jewish community about World War II were collected. The peculiarity of the circumstances in which the entire population of the Kingdom of Yugoslavia was found is reflected in the fact that at the beginning of the war, the country was occupied by five invaders: Germany, Italy, Bulgaria, Hungary, Albania and the fascist satellite formation, the so-called. The Independent State of Croatia. These circumstances also led to different ways of surviving and rescuing Jews from these areas. The Jewish Historical Museum of the Federation of Jewish Communities of Yugoslavia / Serbia published these books with help of donations and volunteer work of the editorial board in which seven of nine members survived the Holocaust. These books are an extraordinary collection of tragic and dramatic experiences about unique choices - the struggle for life, dignity, and freedom in partisans; about concentration camps, about refugee life under constant threat, about help and friendships. They are also a good basis for exploring the Holocaust and the history of Jews from the former Yugoslavia. Each testimony is enriched with a series of photographs and together with the text, they make unique documentation material. As the suffering of Jews on the territory of the former Yugoslavia is poorly known to the general public, these books have the task of filling that space. They thus become a memorial for all the victims whose many names are found only in memory. One of those memories is "Dr. Alfred Najfeld - conversations with our father" by Igor and Vesna Najfeld

Dr. Alfred Najfeld - conversations with our father

U seriji od pet knjiga "Mi smo preživeli: Jevreji o Holokaustu" od kojih su tri prevedene na engleski jezik, sakupljena su svedočenja malobrojnih preživelih članova jevrejske zajednice o vremenu Drugog svetskog rata. Osobenost prilika u kojima se zateklo celokupno stanovništvo Kraljevine Jugoslavije ogleda se u činjenici da je tu državu, početkom rata, okupiralo pet zavojevača: Nemačka, Italija, Bugarska, Mađarska, Albanija i fašistička satelitska tvorevina, tzv. Nezavisna država Hrvatska. Te okolnosti su uslovile i različite načine preživljavanja i spašavanja Jevreja sa ovih prostora. Jevrejski istorijski muzej Saveza jevrejskih opština Jugoslavije/Srbije objavio je ove knjige uz pomoć donacija i uz volonterski rad redakcije u kojoj je sedam od devet članova preživelo Holokaust. One čine izuzetnu kolekciju tragičnih i dramatičnih iskustava o jedinstvenom izboru – borbi za život, dostojanstvo i slobodu u partizanima; o koncentracionim logorima, o izbegličkom životu pod stalnom pretnjom, o pomoći i prijateljstvima. One su i dobra podloga za istraživanje Holokausta i istorije Jevreja sa tla bivše Jugoslavije. Svako svedočenje je obogaćeno nizom fotografija i zajedno sa tekstom čine jedinstveni dokumentacioni materijal. Kako je stradanje Jevreja na tlu bivše Jugoslavije slabo poznato široj publici, ove knjige imaju zadatak da ispune taj prostor. One tako postaju spomenik za sve stradale čija se mnogobrojna imena nalaze samo u sećanjima. Jedno od tih sećanja je "Dr Alfred Najfeld - sećanje na razgovore sa našim ocem" Igora i Vesne Najfeld.In five books, "We Survived: Yugoslav Jews on the Holocaust" (three of them translated into English), the testimonies of a small number of surviving members of the Jewish community about World War II were collected. The peculiarity of the circumstances in which the entire population of the Kingdom of Yugoslavia was found is reflected in the fact that at the beginning of the war, the country was occupied by five invaders: Germany, Italy, Bulgaria, Hungary, Albania and the fascist satellite formation, the so-called. The Independent State of Croatia. These circumstances also led to different ways of surviving and rescuing Jews from these areas. The Jewish Historical Museum of the Federation of Jewish Communities of Yugoslavia / Serbia published these books with help of donations and volunteer work of the editorial board in which seven of nine members survived the Holocaust. These books are an extraordinary collection of tragic and dramatic experiences about unique choices - the struggle for life, dignity, and freedom in partisans; about concentration camps, about refugee life under constant threat, about help and friendships. They are also a good basis for exploring the Holocaust and the history of Jews from the former Yugoslavia. Each testimony is enriched with a series of photographs and together with the text, they make unique documentation material. As the suffering of Jews on the territory of the former Yugoslavia is poorly known to the general public, these books have the task of filling that space. They thus become a memorial for all the victims whose many names are found only in memory. One of those memories is "Dr Alfred Najfeld - sećanje na razgovore sa našim ocem" (Dr. Alfred Najfeld - conversations with our father) by Igor and Vesna Najfeld