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Deletion 13q [del(13q)] is a favorable prognostic marker if it is detected as a sole abnormality in chronic lymphocytic leukemia (CLL). However the clinical courses of cases with isolated del(13q) are quite heterogeneous. In our study, we investigated copy number variations (CNVs), loss of heterozygosity (LOH), and the size of del(13q) in 30 CLL patients with isolated del(13q). We used CGH+SNP microarrays in order to understand the cause of this clinical heterogeneity. We detected del(13q) in 28/30 CLL cases. The size of the deletion varied from 0.34 to 28.81 Mb, and there was no clinical effect of the deletion size. We found new prognostic markers, especially the gain of 16p13.3. These markers have statistically significant associations with short time to first treatment and advanced disease stage. Detecting both CNVs and LOH at the same time is an advantageous feature of aCGH+SNP. However, it is very challenging for the array analysis to detect mosaic anomalies. Therefore, it is very important to confirm the results by FISH. In our study, we detected approximately 9% mosaic del(13q) by microarray. In addition, the gain of 16p13.3 may affect the disease prognosis in CLL. However, additional studies with more patients are needed to confirm these results.

Chronic lymphocytic leukemia (CLL) is known as type of leukemia originating from clonal mature B lymphocytes and has genetic heterogeneity. Many studies have been done to clarify the genome of CLL. In these studies, del(13q) is reported as the most common chromosomal aberration. Although this anomaly is associated with good prognosis when isolated, patients have clinical heterogeneity. In addition, in many gene mutations including TP53, NOTCH1 and SF3B1 gene mutations, poor prognosis has been identified. The prognostic significance of these genes has begun to be demonstrated. According to these data, we aimed to determine the mutation rate of NOTCH1 and SF3B1 genes and to investigate the prognostic effects (disease stages, TTFT and OS) in 43 cases with isolated del(13q) by using FISH method. We investigated the most common mutations of NOTCH1 and SF3B1 gene in CLL by using Sanger sequencing method. While frameshift 7541_7542delCT mutation was detected in the NOTCH1 gene in 1 out of 42 CLL cases with clinical heterogeneity, mutation in the SF3B1 gene couldn’t be detected. As a result of our study, it was observed that NOTCH1 and SF3B1 gene mutations weren’t associated with isolated del(13q) which is compatible with the literature data. Our study is the first study that evaluates NOTCH1 and SF3B1 gene mutations with prognostic parameters of isolated del(13q) with CLL patients in the Turkish population. As a result; It was concluded that there may be different reasons responsible for the clinical heterogeneity of isolated del(13q) cases and further studies are needed to reveal these reasons, Kronik lenfositik lösemi (KLL) klonal matür B lenfositten kaynaklanan ve genetik heterojenite gösteren bir lösemi tipi olarak bilinmektedir. KLL’nin genomunun aydınlatılması için birçok çalışma yapıldığı görülmektedir. Bu çalışmalarda, kromozomal aberasyonlardan en sık del(13q)’nun meydana geldiği bildirilmektedir. Bu anomali izole olduğu durumda iyi prognoz ile ilişkilendirilmesine rağmen, hastalar klinik heterojenite göstermektedir. Bunun yanında kötü prognoz ile ilişkilendirilen TP53, NOTCH1 ve SF3B1 gen mutasyonlarının da bulunduğu bir çok gende mutasyonlar tanımlanmış ve prognostik önemleri ortaya koyulmaya başlanmıştır. Biz de, bu veriler doğrultusunda FISH yöntemiyle izole del(13q) saptadığımız 43 olguda NOTCH1 ve SF3B1 genlerinin mutasyon oranını belirlemeyi ve prognoza (hastalık evreleri, TTFT ve OS) olan etkisini araştırmayı hedefledik. KLL’de en sık gözlenen NOTCH1 ve SF3B1 gen mutasyonlarını Sanger sekanslama yöntemi ile araştırdık. Klinik heterojeniteye sahip KLL olgu grubumuzun, 1/42’sinde NOTCH1 geninde frameshift 7541_7542delCT mutasyonu saptanırken, SF3B1 geninde mutasyon tespit edemedik. Çalışmamız sonucunda, NOTCH1 ve SF3B1 gen mutasyonlarının literatür verileri ile uyumlu olarak izole del(13q) ile ilişkili olmadığı gözlenmiştir. Çalışmamız Türk populasyonunda izole del(13q) KLL hastalarında prognostik parametreler ile birlikte NOTCH1 ve SF3B1 gen mutasyonlarının değerlendirildiği ilk çalışma olma özelliğindedir. Sonuç olarak; izole del(13q) vakalarının klinik heterojenitesinden sorumlu başka nedenlerin de olabileceği ve bunların ortaya çıkarılmasını amaçlayan daha fazla çalışmaya ihtiyaç olduğu sonucuna varılmıştır.

Background: deletion of 13q14 [del(13q)] is the most common cytogenetic change (50%) in chronic lymphoblastic leukemia (CLL), and it is a good prognostic factor if it is detected as a sole aberration by FISH. However, it is observed the clinical course of CLL cases with del(13q) are quite heterogeneous and the responsible for this clinical heterogeneity has not been established yet. Some investigators suggest type II deletion (include RB1 gene) is associated with more aggressive clinical course. Also, it is suggested that the deletion burden and the deletion type have a prognostic effect. In this study, we aimed to investigate the effect of RB1 gene deletion, deletion burden and deletion type on overall survival (OS), disease stage and time to first treatment (TTFT) in patients with isolated del(3q). Sixty eight cases, detected isolated del(13q) were included in the study. Also, RB1 deletion was analyzed from peripheral blood of them using FISH. Results: RB1 deletion was detected in 41% of patients, but there was no statistically significant difference between RB1 deletion and TTFT, stage and OS (p > 0.05). At same time, statistically significant difference was detected between high del(13q) (> 80%) and TTFT (p < 0.05). Conclusion: the statistical analysis of our data regarding to the association between RB1 deletion and deletion type, TTFT, disease stage, and OS has not confirmed type II deletion or biallelic deletion cause poor prognosis. However, our data supports the deletion burden has a prognostic effect. More studies are needed to elucidate the cause of the clinical heterogeneity of CLL cases with del(13q)., Turkish Society of Hematology

In acute myeloid leukemia, t(8;21) detected with a frequency of 10% is associated with good prognosis. However, variant t(8;21) is observed in 4% of these cases, and although the prognostic effects of these variant translocations have not been clearly revealed, there are findings that they affect the prognosis poorly. Here, we report on a 39 years old man, detected 4-way varyant t(8;21) which include relocalization of RUNX1/RUNX1T1 fusion gene, and loss of Y chromosome. RT-PCR also confirmed RUNX1/RUNX1T1 fusion transcript. Additionally, D820G and N822K mutations on KIT gene and mut B on NMP1 gene were detected. A complete remission could not achieved after first chemotherapy treatment. Due to primary resistance and variant of t(8;21), stem cell transplantation was performed. The variant translocation we have reported is unique and also the case is the second case that was reported in the literature in terms of the relocation of the AML1/ETO fusion gene. Since c-KIT mutations and LOY were also observed, it is not possible to predict the prognosis. To highlight the importance of variant translocations and relocalization of fusion gene, more cytogenetic and molecular data are needed.