Erdinç Yüksel

Microsatellite instability in early-onset breast cancer

Breast cancer in a young person is considered a rare and very aggressive disease. The theories addressing the underlying genetic mechanisms of this disease are controversial. Therefore, additional genetic concepts playing a possible role in its pathogenesis and prognosis must be investigated. Microsatellite instability (MSI) characterized by a mutational process of insertions or deletions in microsatellite repeats might constitute a sensitive indicator for genomic instability in cancer. MSI has been described in a wide variety of tumors, particularly in hereditary non-polyposis colorectal cancer. The reports regarding its occurrence and prognostic significance in breast cancer are in conflict with each other. The purpose of this study was to investigate MSI in early-onset breast cancer and to correlate its occurrence with clinicopathological prognisticators. In this study, 16 female patients with primary breast cancer under 35 years of age (range 29-34) were investigated for the incidence of MSI in five microsatellite loci (D2S123, D3S1611, D17S807, D17S796 and Xq11-12) by comparing paired normal and tumor tissue DNA after PCR amplification from paraffin-embedded tissues. No instability was found in any of these five microsatellite loci. Although care must be taken not to overstate the importance of this result due to the inadequate number of microsatellite markers and DNA samples studied, this preliminary report indicates that MSI phenotype is uncommon in human early-onset breast cancer. Therefore, it does not appear to be related to the prognosis of disease.

Development of Acute Promyelocytic Leukemia with Isochromosome 17q after BCR/ABL Positive Chronic Myeloid Leukemia

We describe a pediatric case of acute promyelocytic leukemia with an i(17q) after treatment of BCR/ABL positive chronic myeloid leukemia (CML) for 3.5 years. The patient was treated with Busulphan, alpha-2a interferon, hydroxyurea, and cytosine arabinoside at various times in the course of the chronic phase of CML, because he had no HLA-identical donor for bone marrow transplantation. Hematologic remission was achieved for a short time, but cytogenetic remission was never possible. When promyelocytic blast crisis was diagnosed according to the French-American-British classification, cytogenetic studies revealed an i(17q) as a new feature in our patient. The promyelocytic transformation was associated with the appearance of an i(17q) preceding CML are discussed in the light of recent literature.

The clinical, haematological and morphological profile of patients with myelodysplastic syndromes : A single institution experience from Turkey

In a retrospective analysis of 113 patients with primary myelodysplastic syndromes (MDS) diagnosed according to French-American-British (FAB) classification, we evaluated the prognostic impact of FAB and World Health Organisation (WHO) classifications, International Prognostic Scoring System (IPSS), and other clinical and laboratory variables. The median age was 69. IPSS could be applied to 75 patients classified according to the FAB criteria and to 50 patients reclassified according to the WHO criteria. At a median follow-up of 24 months, 22 patients (19.5 %) transformed to acute myelogenous leukaemia (AML). Overall survival (OS) of patients differed significantly between the FAB and WHO subgroups (p < 0.0001). In WHO classification, significant differences were observed in both OS and leukaemia free survival (LFS) between patients with RA/RARS and refractory cytopenia with multi-lineage dysplasia/refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts (RCMD/RS-RCMD) (p = 0.0001). High-risk according to IPSS score and blood transfusion need were significantly predictive for a shorter survival and higher risk of transformation. Hemoglobin <10 g/dl, neutrophil count <0.5 × 109/L, platelet count <50 × 109/L had an unfavourable prognostic impact on survival in multi-variate analysis. Our conclusions support the previous findings on the value of WHO classification for prediction of prognosis in MDS.

Rapid transformation of atypical myeloproliferative disorder with consistent t(8;13) to B-cell acute lymphoblastic leukemia: A case report

Abstract 8p11 myeloproliferative syndrome (EMS; also known as the stem cell leukemia syndrome-SCLL) is a rare atypical myeloproliferative disorder associated with chromosomal abnormalities involving the 8p11 chromosomal band. Translocations associated with this syndrome result in the fusion of the fibroblast growth factor receptor 1 (FGFR 1) gene with various partners, resulting in ligand independent FGFR activity. The most commonly observed translocation of this syndrome is t(8;13), which results in the expression of a chimeric ZNF198-FGFR1 tyrosine kinase. Disease phenotype associated with this translocation has some typical features such as poor prognosis, and transformation to mainly acute leukemia and non-Hodgkin lymphoma; commonly with a T-cell phenotype in which obtaining and maintenance of remission is difficult by conventional chemotherapy. We hereby present a case diagnosed as atypical chronic myeloproliferative disease with consistent t(8;13)(p12;q12) and transformed rapidly to pre-B-cell acute lymphoblastic leukemia which is a rare clinical presentation.

Isolated myelosarcoma development in an adolescent chronic myeloid leukemia patient with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).

Additional chromosomal abnormalities are found in 5-20% of patients during chronic phase of chronic myeloid leukemia and in 60-80% preceding or accompanying blast crisis. These abnormalities are important in disease progression and, because they may occur before hematological and clinical symptoms, can be taken as a prognostic indicator. An adolescent with chronic myeloid leukemia initially presented with extreme thrombocytosis, increased megakaryopoiesis with dysmorphic features, and focal myelofibrosis in bone marrow examinations and then developed isolated myelosarcoma 1 year after onset, with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).

Mozaik Turner Sendromlu Olguda Anestezi Yaklaşımı (Literatür Taramasıyla Olgu Sunumu)

Mozaik turner sendromu (TS) buyume geriligi, gonadal disgenezi ve infertilite ile karakterize kromozomal endokrin bir bozukluktur. 45, X/46, XX kromozomal patern hastaligin en sik rastlanan mozaik tipidir (%36). Turner sendromunda yeniden duzenlenmis X kromozomunun oldugu durumlar tolere edilebilir. Ancak X halka kromozomu ve X otozom translokasyonlarinda mental retardasyon ve konjenital anomalilerin insidansi belirgin sekilde artmistir. Bu anormal fenotipler bozulmus veya kismi inaktivasyona ugramis X kromozomuna baglidir. Biz burada 22 yasinda kolesistektomi ve tiroidektomi gecirmis, sitogenetik analiz yapilmis turner sendromlu olguyu rapor ettik. Turner sendromunun triatlarina uygun kisa boylu ve normal zekali olan hastanin sitogenetik analiz sonucunda 45,X[10]/46,XX[75] mozaik karyotipi goruldu. Beraberinde tasidigi anomalilerden dolayi anestezik acidan onemli sayilan sorunlara yola acan mozaik turner sendromlu olguda operasyonlarda izlenecek anestezi yaklasimini gozden gecirmeyi amacladik

İmatinib Mesilat ile Tedavi Edilen Kronik Myeloid Lösemi Vakalarında Belirlenen Trizomi 8

Kronik myeloid losemi vakalarinda t(9;22)(q34;q11) translokasyonu sonucu Philadelphia (Ph) kromozomu olusmakta ve bu translokasyon bcr-abl gen fuzyonuna yol acmaktadir. Imatinib mesilat (STI571, Glivec) bcr-abl gen fuzyonu sonucu sentezlenen bcr-abl tirozin kinaz proteininin inhibitorudur. Ileri faz kronik myeloid losemi vakalarinda en sik gozlenen sekonder karyotipik anomaliler, ikinci Ph, trizomi 8, izokromozom 17q ve trizomi 19 dur. Cok sayida vakada Ph(-) ve Ph(+) hucrelerde klonal karyotipik anomaliler gelismektedir. Bu calismada imatinib mesilat ile tedavi edilmis biri Ph(-) trizomi 8, ucu de Ph(+) trizomi 8 olmak uzere dort vaka rapor edilmektedir