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Kronik myeloid lösemi tedavisinde kullanılan imatinib mesilat aynı zamanda kök hücre faktörünü de inhibe etmektedir. Imatinib mesilatın bazı polistemia veralı hastalarda otonom eritroid koloni gelişimini inhibe ettiği ve flebotomi ihtiyacını azalttığı da gösterilmiştir. Bu çalışmada, imatinib mesilat varlığında, polistemia veralı üç hasta ile sağlıklı dört kontrolden elde edilen periferik kan eritroid öncül hücreleri üzerine yarı-katı ortamda insülin benzeri büyüme faktörü-l (IGF-l), kök hücre faktörü (SCF) ve eritropoietin (EPO) ile interlökin-3 (IL-3), granülosit-koloni stimule edici faktörün (GM-CSF) ve granülosit-koloni stimule edici faktörünün (G-CSF) etkisi araştırıldı. Sağlıklı kontrollerden elde edilen hematopoietik öncü hücrelerden eritroid koloni gelişimi sadece tüm sitokinlerin varlığında gözlendi. Bununla birlikte eritroid kolonilerin sayısı polistemia veralı hastalardan elde edilen sayılara ulaşamadı. Imatinib mesilatın eritroid koloni gelişimi üzerindeki inhibe edici etkisi belirgindi. Polistemia veralı hastaların hematopoietik öncüllerinden iki tip eritroid koloni gelişimi gözlendi; ilki eksojen sitokinlerden bağımsız ve sitokinlere aşırı duyarlılık gösteren, ikincisi ise eksojen sitokinlere aşırı duyarlılık gösteren tip idi. Her iki tipte de IL-3, GM-CSF ve EPO de dahil olmak üzere, sitokinlerin varlığında imatinib mesilatın inhibe edici etkisi belirgindi. Imatinib mesilatın bu etkisinin IL-3, G-CSF, GM-CSF, EPO ve IGF-l üzerine olduğunu söylemek için henüz yeterli kanıt yoktur. Bu çalışmanın sonuçları daha önceki çalışmalardan elde edilen bilgilerle birlikte değerlendirildiğinde, imatinib mesilatın eritroid koloni gelişimini inhibe edici etkisinin kök hücre faktörünün ve reseptörlerinin rol aldığı sinyal ileti yolları üzerinden olduğu söylenebilir.

It has been shown that imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia, inhibits the effect of stem cell factor, which has a central role in erythropoiesis. In some polycythemia vera (PV) patients, it has inhibited autonomous erythroid colony growth in vitro and decreased the need for phlebotomy. In this study we have investigated the effect of insulin like growth factor (IGF)-I, stem cell factor (SCF) and erythropoietin (Epo) with interleukin (IL)-3, granulocyte macrophage-colony stimulating factor (GM-CSF) and granulocyte-colony stimulating factor (G-CSF) in the presence of imatinib mesylate on the erythroid progenitors derived from peripheral blood mononuclear cells of three patients with PV and four healthy controls in semisolid medium. Erythroid colony formation from hematopoietic progenitors obtained from healthy controls was observed only in the presence of all cytokines. However, the number of erythroid colonies could not reach that of patients with PV. Inhibition of imatinib mesylate on erythroid colony growth was evident. Hematopoietic progenitors of patients with PV displayed two types of colony formation: the first type was exogenous cytokine-independent and was hypersensitive to current cytokines, and the second displayed hypersensitivity to current exogenous cytokines, but was exogenous cytokine-dependent. For both types, the inhibitory effect of imatinib mesylate was striking in the presence of all cytokines including IL-3, GM-CSF and Epo. There is no direct evidence yet that imatinib mesylate could inhibit the effect of IL-3, G-CSF, GM-CSF, Epo and IGF-I on erythropoiesis. Considering former studies together with results of this study, it can be argued that imatinib mesylate is effective in PV on the intersecting signal transduction mechanisms in which stem cell factor and its receptor may have a part.

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Periferik kanda lökosit sayısının ≥100x109/L olması ile karakterize hiperlökositozis, çocukluk çağı lösemilerinde %5-20 oranında görülebilen ve prognozu kötü olarak etkileyen bir risk faktörüdür. Bu çalışmada, 1 Ocak 1990-1 Ocak 2001 tarihleri arasında İzmir’deki 4 merkezde tanı alıp tedavi edilmiş ve tanı sırasında hiperlökositoz saptanmış 47 akut lenfoblastik lösemili (ALL) çocuğun klinik ve laboratuvar bulguları, gelişen komplikasyonlar ve sağkalımlarının araştırılması amaçlandı. Olguların ortanca yaşı 5.0 yaş (0,1-16,3 yaş) idi. Ortanca beyaz küre sayısı 495x109/L (107x109/L-794x109/L) bulundu. Tanı anında olguların 42’sinde (%90) hepatosplenomegali, 5’inde (%11) respiratuvar distres, 3’ünde (%6) nörolojik semptomlar, 3’ünde (%6) diffuz servikal lenfadenopati, 3’ünde (6%) akut böbrek yetmezliği bulguları vardı. On olguda (%21) santral sinir sistemi, 17 olguda (%36) mediastinal tutulum mevcuttu. Tedavi başlamadan önce 10 olguda (%21) koagulopati, 15 olguda (%32) metabolik bozukluk (8 olguda hiperürisemi, 4 olguda hiperfosfatemi, 2 olguda hiperürisemi, hiperfosfatemi ve hiperkalsemi, 1 olguda hipokalsemi) saptandı. 40 olguda (%85) intravenöz hidrasyon, alkalinizasyon ve allopurinol tedavisi ile hiperlökositoz kontrol altına alındı. İndüksiyon tedavisinin ilk 15 gününde 5 olgu (%11) respiratuvar distres ve sepsisle kaybedildi. Olguların hastalıksız ve genel sağkalımlarının sırasıyla %37,0 ve %40,5 olduğu saptandı.

Hyperleukocytosis, defined as a peripheral leukocyte count ≥ 100x109/L, is seen in 5-20% of newly diagnosed cases of childhood leukemia and is a poor prognostic factor. In this study, we aimed to examine the presenting clinical and laboratory features, complications, and treatment outcome of 47 children with acute lymphoblastic leukemia (ALL) and hyperleukocytosis who were diagnosed and treated in four medical centers of İzmir between January 1990 and January 2001. The median age was 5.0 years (range: 0.1-16.3 years). Median white blood cell count was 495x109/L (range: 107x109/L- 794x109/L). Forty-two of 47 patients (90%) had hepatosplenomegaly, 5 (11%) had respiratory distress, 3 (6%) had neurologic symptoms, 3 (6%) had diffuse cervical lymphadenopathy, and 3 (6%) had acute renal failure at admission. Ten of 47 patients (21%) had central nervous system involvement, and 17 (36%) had mediastinal mass. Ten patients (21%) had coagulopathy and 15 patients (32%) had metabolic complications (8 patients had hyperuricemia, 4 had hyperphosphatemia, 2 had hyperuricemia, hyperphosphatemia and hypercalcemia, and 1 had hypocalcemia) before the initiation of therapy. Forty of 47 patients (85%) with hyperleukocytosis were effectively managed with intravenous hydration, alkalinization, and allopurinol therapy. Early death during remission induction therapy occurred in 5 patients (11%) with respiratory distress and sepsis. Kaplan-Meier estimates of event free survival and overall survival were 37.0% and 40.5%, respectively.

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The incidence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Iran is around 10-14.9%. G-6-PD deficiency is an X-linked recessive disorder that is more prevalent in males. In our area, 80% of blood donors are males. At present, pre-donation data are relied on for detecting diseases in Shiraz blood banks and the donors’ blood is not routinely screened for G-6-PD deficiency. Transfusion of such blood may induce hemolysis in recipients, especially in premature neonates and in neonates having exchange transfusion. Four hundred and fifty blood bags in a blood bank of Shiraz from male donors were enrolled in this cross-sectional study. The blood samples were tested with fluorescent spot test for G-6-PD deficiency. G-6-PD-deficient donors were identified, and if they agreed, were asked to participate in the study. Each volunteer filled out a questionnaire. From 450 blood bags, 27 bags were G-6-PD deficient (6%). Only 19 donors could be traced who volunteered to participate in the study. Two donors (10%) had positive past history of hemolysis. Ten donors (52.6%) had positive family history of hemolysis (red urine and jaundice) when exposed to fava beans, mothballs, aspirin or other drugs. Nine donors had a male member in the family with hemolysis and one had a female relative with hemolysis. Five donors (26.3%) had positive history of neonatal jaundice. According to this study, 52% of donors had a positive family history of hemolysis, but only 10% had positive history of hemolysis themselves; therefore, addition of past history and family history of hemolysis has a good predictive value in detection of the G-6-PD-deficient donors.

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B-cell acute lymphoblastic leukemia (B-ALL) accounts for 20-30% of acute leukemias in adults. Combined application of data from immunophenotyping, karyotyping and molecular analyses allows a better understanding of this heterogeneous disease. We studied 30 adult patients with newly diagnosed B-ALL by conventional cytogenetics, fluorescent in situ hybridization (FISH) and immunophenotyping analyses. We report statistically significant prevalence of structural aberrations (43%) over numerical changes (17%) (p=0.02). The most frequent structural changes were t(9;22)(q34;q11)/bcr-abl-17%, t(8q24)/C-MYC-10%, t(11q23)/MLL-6%, del 4p-6%, del12p-3%, and t(1;19)-3%. Complex karyotype was found in 17% and normal karyotype in 30%. The most frequent immunophenotype was of common B-ALL (43%), and cytogenetic and/or molecular abnormalities were found in 78% of them. We distinguished a relatively high incidence (17%) of mature B-ALL and 60% of them were associated with t(8;14)/C-MYC. We established association of cytogenetic aberrations with immunophenotype only in mature B-ALL. The other immunophenotypes are characterized by genetic heterogeneity and the presence of cytogenetic abnormalities unusual for adult B-ALL - trisomy 8 and t(1;19)(q23;p13).

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Objective of the study is the retrospective evaluation of clinico-hematological and cytogenetic profile of patients with erythroleukemia (EL) in a south Indian population. Case records of all patients with acute myeloid leukemia seen in the Department of Medical Oncology at Kidwai Memorial Institute of Oncology, Bangalore, between January 1997 and December 2004 were reviewed. Clinical details were noted and slides were reviewed. A total of 326 AML patient were diagnosed of whom 14 patients had AML M6. Contribution of EL to all forms of AML was 4.3%. The mean age was 37.1+13.9 yrs (range: 16-65); most patients were in their 4th decade, with a male: female ratio of 3.67: 1. Mean duration of symptoms in the present series was 10.9+6.9 weeks. Cytogenetics were normal in 71% of cases, and minor abnormalities were observed in 21% of cases. As a conclusion relative low incidence of secondary EL, more frequent normal karyotype, and relatively younger age observed in our series makes the picture of EL in our subcontinent different from that in other series reported thus far.

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Hb J-Iran [beta77(EF1)His-Asp] herhangi bir sağlık sorunu yaratmayan nadir hemoglobin türlerinden olup Türkiye’de ilk kez 1986 yılında bildirilmiştir. Bu çalışmada sunulan heterozigot olgu ülkemizde bildirilen dördüncü, Denizli yöresinde ise ilk olgu olma özelliğini taşımaktadır.

Hb J-Iran [beta77(EF1)His-Asp], a rare hemoglobin variant that does not present health problems, was reported for the first time in the Turkish population in 1986. Our case is the fourth case reported in Turkey and the first case from the Denizli province.

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