Additional cytogenetic aberrations in chronic myeloid leukemia: a single-center experience in the Middle East

BACKGROUND: Additional cytogenetic aberrations are associated with disease progression in chronic myeloid leukemia (CML). This study was conducted to determine the type and frequency of these aberrations and their relationship with hematologic and molecular findings in the Middle East. METHODS: In this retrospective study, 134 well-established cases of CML were selected from 2010 to 2016. Their hematologic phase and type of fusion gene were determined. Finally, their karyotypes were analyzed and reported according to ISCN 2013. RESULTS: Patients had a mean age of 44 years. Twenty-two patients (16.4%) showed additional cytogenetic aberrations. Nine patients (6.7%) harbored a variant Philadelphia chromosome, and most were in the chronic phase. Seventeen patients (12.7%) had major and minor route abnormalities. There was a significant relationship between additional cytogenetic aberrations and major molecular response (P=0.032). Patient survival in the group with additional cytogenetic aberrations was significantly lower (49.7±11.1 mo) than that in the group without additional cytogenetic aberrations (77.3±3.1 mo) (P=0.031). CONCLUSION: This study revealed the same frequency of additional cytogenetic aberrations in CML as found in previous studies. Additional chromosomal aberrations led to shorter survival and lower rates of achievement of a major molecular response.

A rare variant of t(17;19) in a case of Philadelphia positive adult acute lymphoblastic leukemia presenting with disseminated intravascular coagulation

No abstract available.

[Plexiform angiomyxoid myofibroblastic tumor in a 38 years old man]

Plexiform angiomyxoid myofibroblastic tumor is a very rare mesenchymal tumor of stomach which is diagnosed based on morphologic findings such as plexiform growth pattern, spindle cell proliferation in a myxoid background, by aiding immunohistochemistry staining and ruling out of other mesenchymal gastric tumors. We report this tumor with about 4cm size in antrum of a 38 years old man which endoscopic and CT scan results fit with Gastrointestinal stromal tumor and diagnoses is performed according to specific morphologic and immunohistochemistry findings

Dicer gene expression as a prognostic factor in acute lymphoblastic leukemia and chronic lymphocytic leukemia in pars province

Alterations in the expression of microRNAs [miRNAs] have been proposed to play a role in the pathogenesis of acute lymphoblastic leukemia [ALL] and chronic lymphocytic leukemia [CLL]. Dicer is one of the main regulators of miRNA biogenesis, and deregulation of its expression has been indicated as a possible cause of miRNA alterations observed in various cancers. Our aim was to analyze the expression of the Dicer protein and its relationship with ALL and CLL. This cross-sectional study was performed from 2010 to 2012 in Shahid Faghihi Hospital, Shiraz, Iran. In this study, 30 patients with CLL, 21 patients with ALL, 10 child healthy donors, and 19 adult healthy donors were recruited. The patients' samples were checked via flow cytometry, immunohistochemistry, and immunocytochemistry. The controls' samples were also examined in the hematology ward. Total RNA was extracted from the bone marrow and peripheral blood samples of the patients and controls. Then, reverse-transcription polymerase chain reaction was used to estimate the level of Dicer miRNA. The outcomes of the expression analysis of Dicer revealed statistically significant differences between the ALL patients/child healthy controls [meaniSD, 0.19 +/- 0.28vs. 0.73 +/- 0.12; P<0.001] and the CLL patients/adult healthy controls [mean +/- SD, 0.24 +/- 0.25 vs. 0.41 +/- 0.28; P=0.033]. This is the first piece of evidence showing that the expression of the Dicer gene greatly decreased in the patients with ALL in comparison to the child controls. The expression of the Dicer gene was also downregulated in the patients with CLL compared to the adult controls. Given the above findings, the expression of Dicer may play an important role in the progression and prognosis of these diseases

Does the relief of glucose toxicity act as a mediator in proliferative actions of vanadium on pancreatic islet beta cells in streptozocin diabetic rats?

Data shows vanadium protects pancreatic beta cells [BC] from diabetic animals. Whether this effect is direct or through the relief of glucose toxicity is not clear. This study evaluated the potential effect of oral vanadyl sulfate [vanadium] on glycemic status and pancreatic BC of normal and diabetic rats. Rats were divided into five groups of normal and diabetic. Diabetes was induced with streptozocin [40 mg/kg, i.v.]. Normal rats used water [CN] or vanadium [1 mg/ml VOSO4, VTN]. Diabetic rats used water [CD], water plus daily neutral protamine Hagedorn insulin injection [80 U/kg, ITD] or vanadium [VTD]. Blood samples were taken for blood glucose [BG, mg/dL] and insulin [ng/dL] measurements. After two months, the pancreata of sacrificed rats were prepared for islet staining. Pre-treated normal BG was 88 +/- 2, and diabetic BG was 395 +/- 9. The final BG in CD, VTD, and ITD was 509 +/- 22, 138 +/- 14, and 141 +/- 14, respectively. Insulin in VTN [0.75 +/- 0.01] and VTD [0.78 +/- 0.01] was similar, higher than CD [0.51 +/- 0.07] but lower than CN [2.51 +/- 0.02]. VTN islets compared to CN had larger size and denser central core insulin immunoreactivity with plentiful BC. CD and ITD islets were atrophied and had scattered insulin immunoreactivity spots and low BC mass. VTD islets were almost similar to CN. Besides insulin-like activity, vanadium protected pancreatic islet BC, and the relief of glucose toxicity happening with vanadium had a little role in this action

Expression status of UBE2Q2 in colorectal primary tumors and cell lines

Background: Activation of the ubiquitin-proteasome pathway in various malignancies, including colorectal cancer, is established. This pathway mediates the degradation of damaged proteins and regulates growth and stress response. The novel human gene, UBE2Q2, with a putative ubiquitin-conjugating enzyme activity, is reported to be overexpressed in some malignancies. We sought to investigate the expression levels of the UBE2Q2 gene in colorectal cell lines as well as in cancerous and normal tissues from patients with colorectal cancer

Methods: Levels of UBE2Q2 mRNA in cell lines were assessed by Real-Time PCR. Western blotting was employed to investigate the levels of the UBE2Q2 protein in 8 colorectal cell lines and 43 colorectal tumor samples

Results: Expression of UBE2Q2 was observed at the level of both mRNA and protein in colorectal cell lines, HT29/219, LS180, SW742, Caco2, HTC116, SW48, SW480, and SW1116. Increased levels of UBE2Q2 immunoreactivity was observed in the 65.11% [28 out of 43] of the colorectal carcinoma tissues when compared with their corresponding normal tissues. Difference between the mean intensities of UBE2Q2 bands from cancerous and normal tissues was statistically significant at P<0.001 [paired t test]

Conclusion: We showed the expression pattern of the novel human gene, UBE2Q2, in 8 colorectal cell lines. Overexpression of UBE2Q2 in the majority of the colorectal carcinoma samples denotes that it may have implications for the pathogenesis of colorectal cancer

Bone marrow and karyotype findings of patients with pancytopenia in southern Iran

Background: Pancytopenia is a manifestation of a wide range of disorders. The main prognostic factor for predicting outcome and response to treatment is based on the underlying cause. To detect the root cause of this problem, depending on other accompanied signs or symptoms, the need for bone marrow examination and other advanced work ups is different at least at the practical level. This study focuses on the karyotype abnormality and to demonstrate the ability of this complimentary study in diagnosis and prognosis of such patients

Methods: In this cross sectional study, bone marrow aspiration samples of all patients with Pancytopenia underwent cytogenetic investigation on bone marrow aspiration. Gathered data were analyzed by SPSS software

Results: Among the 100 eligible patients, 67% revealed hypercellular, 19% had hypocellular and 13% had normocellular marrow. Most common causes of pancytopenia were myelodysplastic syndrome [MDS] [33%], MDS vs. megaloblastic anemia [23%] and acute leukemia [18%]. Thirty one patients had karyotype abnormality in which majority [13 patients] were diagnosed as MDS followed by 11 patients with acute leukemia

Conclusion: Beside bone marrow examination, there is a need for more supplementary studies like karyotyping to detect the exact cause of pancytopenia. It is concluded that cytogenetic study on bone marrow aspiration can be a complementary test in diagnosis of pancytopenic patients. However, there are also cases where diagnosis even with implementing bone marrow examination and cytogenetic analysis is not possible. Such patients require more clinical follow-up and investigation

Evaluation of Ki67, p16 and CK17 markers in differentiating cervical intraepithelial neoplasia and benign lesions

Background: Cervical intraepithelial neoplasia [CIN] is a premalignant lesion capable of progressing to cervical cancer. Despite the existing well-defined criteria, the histomorphologic diagnosis is subject to high rates of discordance among pathologists. The aim of this study was to evaluate Ki-67 [MIB- 1], CK17 and p16 [INK4a] [p16] markers by immunohistochemical methods in differentiating CIN from benign cervical lesions

Methods: The present study reviewed and re-classified 77 cervical biopsies, originally diagnosed as 31 non-CIN, and 46 CIN, as 54 non-CIN, and 23 CIN based on at least two similar diagnoses. Immunostaining by Ki67, p16 and CK17 markers was performed on all cases and the results were compared with pervious and consensus diagnosis

Results: The overall agreement between pervious and consensus diagnosis was 67.5% [Kappa=0.39, P<0.001]. The sensitivity and specificity of Ki67 immunostaining were 95.6% and 85.1% respectively, while for p16 the corresponding values were 91.3% and 98.1%. The overall agreement, for both p16 and Ki67, with consensus diagnosis were significant [P<0.001]. The sensitivity and specificity of CK17 negative staining in CIN detection were 39.1% and 40.7% respectively

Conclusion: Ki67 and p16 markers are recommended as complementary tests for differentiating between dysplastic and non-dysplastic lesions. CK17 does not discriminate between immature metaplasia with and without dysplasia

Cytogenetic findings of patients with acute lymphoblastic leukemia in Fars province

Background: Acute lymphoblastic leukemia [ALL] is the sixth most common malignancy in Iran. Cytogenetic analysis of leukemic blasts plays an important role in classification and prognosis in ALL patients. The purpose of this study was to define the frequency of chromosomal abnormalities of ALL patients in adults and children in Fars province, Iran

Methods: In this cross-sectional study, we evaluated karyotype results of bone marrow specimens in 168 Iranian patients with ALL [154 B-ALL and 14 T-ALL] in Fars Province using the conventional cytogenetic G-banding method

Results: The frequency of cytogenetic abnormalities, including numerical and/or structural changes, was 61.7% and 53.8% in the B-ALL and T-ALL patients, respectively. Hyperdiploidy was the most common [32%] cytogenetic abnormality. Among structural abnormalities, the most common was t[9;22] in 11% of the patients. The children showed a higher incidence of hyperdiploidy and lower incidence of t[9;22] than adults [P<0.05]. We found a lower incidence of recurrent abnormalities such as 11q23, t[1;19], and t[12;21] than those reported in previous studies

Conclusion: Normal karyotype was more frequent in our study. The frequencies of some cytogenetic abnormalities such as hyperdiploidy and t[9;22] in our study were comparable to those reported in the literature. The results of this study in Fars Province can be used as baseline information for treatment decision and research purposes in ALL patients. We recommend the use of advanced molecular techniques in the future to better elucidate cryptic cytogenetic abnormalities

IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression

CD8+ cytotoxic T lymphocytes have been recently divided based on their cytokine expression profile. To evaluate the percentages of CD8+lymphocytes and their effector subsets including Tc1, Tc2 and Tc17 in the tumor draining lymph nodes [TDLNs] of patients with breast cancer. Single cell suspensions were obtained from TDLNs of 42 patients with breast cancer. Staining of the cell surface markers and intracellular cytokines was performed using appropriate fluorochrome-conjugated antibodies. The data was acquired on a four-color flow cytometer and was analyzed by CellQuestPro software package. The percentages of different CD8+ cell subtypes [Tc1, Tc2 and Tc17] were quantified in CD8+T lymphocytes. The comparison was made between LN+ versus LN- patients, as well as patients in different clinico-pathological status. The percentage of Tc1, Tc2 and Tc17 subsets were not significantly different between LN+ and LN- patients. Despite no difference in the percentages of Tc1 cells in LN+ patients with infiltrative ductal carcinoma [IDC], the mean expression of IFN-gamma by Tc1 cells decreased significantly in comparison to LN- patients. On the other hand, the percentages of Tc2 and Tc17 effector subsets were increased in advanced stages [p=0.018 and p=0.009, respectively]. As the first study to investigate various effector subtypes of CD8+ lymphocytes in TDLNs of patients with breast cancer, our data collectively suggests a positive association between IL-17- and IL-4-producing CD8+ T cell percentages [Tc2 and Tc17] in TDLNs with breast cancer progression. Although the number of Tc1 cells seems not to be affected by cancer progression, down-regulation of IFN-gamma by these cells seems to be associated with tumor metastasis to TDLNs. These findings may have implications in cancer immunotherapy based on CD8+ effector subsets.

Immunohistochemistry study in a case of nephrogenic adenoma of bladder

Nephrogenic adenoma is a rare benign lesion of bladder that may be confused with malignant lesions. There is a strong relation with urinary tract irritation and intravesicle instrumentations. Nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof is available. We present a case of 55-year-old lady with urinary problem. Cystocopic examination showed a sessile mass, and biopsy revealed circumscribed proliferation of tubules, cysts, and papillae that were lined by low cuboidal to columnar epithelial cells. Nephrogenic adenoma can be a significant diagnostic pitfall due to the presence of certain histological features such as the presence of enlarged nuclei with prominent nucleoli. Immunohistochemistery study was strongly positive for CK7, P504S, CD10, and EMA, but negative for CK20, PSA, and P63

Disseminated peritoneal leiomyomatosis

Leiomyomatosis peritonealis disseminate is a very rare condition characterized by the development of multiple smooth muscle-like nodules in the peritoneal cavity. It is associated with increased serum levels of gonadal steroids. The present report describes a Bilateral Salpingo oophorectomy six years ago because of leiomyomatosis peritonealis disseminate. After six years she referred to us again because of retroperitoneal fibroma, another rare entity, during hormone replacement therapy inspite of lack of uterus and previous castration