Myelodysplastic syndromes (MDS) are a group of malignant myeloid hematopoietic disorders. The diagnosis of MDS can be difficult, especially in cases with a low blast count and a normal karyotype. Flow cytometry has been used to distinguish MDS from nonclonal cytopenias. No one single simple flow cytometric parameter has been proposed to be diagnostic of MDS.
The aim of the present study was to evaluate immunophenotypic alterations in typical MDS patients and whether these abnormalities help in the differentiation process between MDS with nonclonal disorder and leukemic patients.
Marrow aspirates from 29 patients, including 13 with MDS, 16 with acute myeloid leukemia, and 18 with nonclonal disorders (normal controls), were examined in this study. Their immunophenotypes were analyzed using flow cytometry. Blasts, nonblast myeloid cells, and monocytes were gated on the basis of CD45 expression and side scatter (SSC).
Comparison among the three groups showed that the granulocytic lineages of MDS showed decreased SSC compared with the controls (P<0.005 and P<0.000, respectively), altered CD45 intensity (P<0.004), decreased CD10-positive granulocytes (P<0.02), and a higher CD56 positive expression in the MDS and leukemic group (P<0.05 and P<0.001, respectively). Also, decreased intensity of CD11b (P<0.03) was observed in the MDS group. The expression rate of CD123+ was significantly higher in MDS patients than that in normal controls (P<0.0001).
Gating of the granulocytic region is a relatively easy method for MDS immunophenotyping. Among the parameters studied, SSC, CD10, CD123, and CD56 were the most useful for differentiating MDS from nonclonal disorders, whereas immunophenotypic changes in MDS appear to be useful for differentiating MDS from nonclonal disorders.
Chronic lymphocytic leukemia (CLL) is an environment-dependent hematologic malignancy where interactions with accessory cells through cytokines and their receptors seem to confer a survival advantage, thus contributing to disease progression. Interleukin-22 (IL-22) is a T-cell-derived cytokine that promotes cell proliferation and survival through interaction with its receptor IL-22RA1, normally absent in normal immune cells, including B and T lymphocytes.
This study aimed to determine the plasma levels of IL-22 and the expression of IL-22RA1 on malignant cells in patients with B-cell CLL (B-CLL), together with their relation to clinical and prognostic characteristics of the disease.
The study was carried out on 62 newly diagnosed B-CLL patients. Twenty-five age-matched and sex-matched healthy individuals served as controls. Patients were diagnosed, according to the International Workshop on CLL guidelines, by cytomophology, immunophenotyping, conventional cytogenetic analysis, and fluorescence in-situ hybridization. Plasma IL-22 levels were measured by an enzyme-linked immunosorbent assay and the expression of IL-22RA1 on leukemic cells was assessed by flow cytometry.
Plasma IL-22 was significantly higher in B-CLL patients (range, undetectable 62.9 pg/ml; median, 6.6) compared with control participants (range, undetectable 6.4 pg/ml; median, undetectable) (P<0.01). IL-22RA1 expression was negative in all normal controls, whereas in B-CLL patients it was positively expressed in 35/62 CLL cases (56%). Taking the median level of IL-22RA1 expression in CLL patients as a cutoff level, overexpression (≥10%) was observed in 32/62 (52%) cases. IL-22RA1 expression correlated significantly positively with plasma levels of IL-22 (rs=0.817; P<0.01). Patients presenting with high CD38 expression had significantly higher plasma IL-22 levels compared with those with low CD38 (undetectable 62.9 pg/ml; median, 19.3 vs. undetectable 50.1 pg/ml; median, 3.1) (P<0.01) as well as overexpression of IL-22RA1. No significant relation could be established between either plasma IL-22 levels or IL-22RA1 expression with other clinical features or prognostic criteria of CLL.
This is the first report to describe the aberrant expression of the IL-22 signaling pathway in B-CLL and to link its overexpression with high CD38 expression, a known poor prognostic marker of the disease.
Transfusion-chelation increased the longevity of patients with β-thalassemia major; thus, puberty and fertility disorders became more apparent.
We aimed to evaluate the pituitary–testicular axis and the progress of puberty after using deferiprone (DFP) and desferrioxamine (DFO) combined chelation in patients with preserved pituitary and testicular functions and to assess the quality of semen analysis in relation to chelation type.
We carried out a 3-year prospective study of pubertal status including 42 polytransfused males (≥14 years) with thalassemia. Patients with delayed puberty were tested for pituitary–testicular axis function. Those with good pituitary and testicular response were shifted to combination chelation. Compliance on chelation and biannual serum ferritin were assessed. Spermiograms were performed at least twice for pubertal males.
The median age of the participants was 20 years at enrollment, and 13 patients (30.9%) had normal puberty; they were on DFP 7/28, DFO 2/10, or combination 4/4 for at least 2 years before enrollment. Of the 29 nonpubertal males, 13 (44.8%) had good pituitary–testicular responses; within 3 years, 8/13 progressed to puberty using the combination chelation. Of the 21 pubertal males, 19 consented to spermiograms, with a low sperm count in 4/19 (21.1%) and poor motility in 6/19 (31.6%) patients, respectively.
Initial evaluation of adolescents and young adult thalassemic males showed that almost two-third were nonpubertal. Combination chelation (DFP and DFO) for those with good pituitary–testicular function led to progression of pubertal development after 3 years in half of them; meanwhile, semen quality was still impaired in one-third of them.
Nucleosomal DNA levels in plasma and serum can be correlated with the extent of cell death at a specific time point. The aim of this study was to evaluate the serum level of nucleosomal DNA fragments as an early predictive marker for acute myeloid leukemia (AML) therapy.
This study included 77 participants: 14 healthy volunteers, included in the control group; they ranged in age between 20 and 55 years, median age 36.5 years. Routine investigations such as liver functions, blood urea, serum creatinine, and complete blood count were performed to confirm their healthy state. The patient group included 63 de-novo AML patients.
In the patient group, serum nucleosome levels ranged between 25 and 760 AU, with a mean±SD of 203.7±197 and a median of 220. In the control group, serum nucleosome levels ranged between 38 and 99 AU, with a mean±SD of 72.8±20.8 and a median of 80; a statistically significant difference was found between nucleosome levels in patients and its level in the control group (P<0.001). In the patient group, the lactate dehydrogenase (LDH) level ranged between 189 and 2088 U/l, with a mean±SD of 714±413 and a median of 829. In the control group, the LDH level ranged between 100 and 430 U/l, with a mean±SD of 231±125 and a median of 195; a statistically significant difference was found between LDH levels in patients and its level in the control group (P<0.001).
It would be valuable to include these markers together with the kinetics of circulating nucleosomal DNA fragments in prospective trials to elucidate their potential additive role in the early prediction of response to therapy. In AML patients, the changes in nucleosomal DNA during the initial phase of induction chemotherapy are valuable markers for the early estimation of therapy response and should be validated in further prospective trials.
B cells play a key role in the pathogenesis of autoimmune diseases by secreting autoantibodies, presenting antigens, and secreting cytokines. Activation of autoreactive B cells is largely mediated by a cytokine called B-cell-activating factor (BAFF), which mediates its signal mainly through BAFF-R. The present study aimed to clarify the impact of BAFF/BAFF-R dysregulation on disease activity and response to therapy in childhood thrombocytopenic purpura (ITP).
Forty-three patients (23 acute and 20 chronic ITP) and 20 age-matched and sex-matched healthy controls were enrolled in this study. Serum BAFF was determined using the enzyme-linked immunosorbent assay technique and the expression of BAFF-R on CD19+ B cells was detected by flow cytometry.
In serum, BAFF level and BAFF-R expression were significantly higher in both acute and chronic ITP patients than in the controls (P⩽0.001). No significant difference was found in the BAFF level and BAFF-R expression between acute and chronic ITP (P=0.456 and 0.124, respectively). After treatment with immunosuppressive therapy, BAFF level and BAFF-R expression were significantly decreased in acute ITP compared with levels before treatment (P⩽0.001). No significant difference was found in the serum BAFF level, whereas BAFF-R expression was significantly higher in active ITP than inactive ITP (P=0.544 and 0.015, respectively).
Our data suggest that BAFF-R is more relevant than serum BAFF as an activity biomarker in ITP patients. It will be interesting to assess the possible implications of this upregulation of BAFF-R on BAFF-targeted therapy in ITP patients, especially those with active disease.
Chronic lymphocytic leukemia (CLL) is one of the most common forms of leukemia and thus research is required to identify cost-effective and efficient prognostic markers.
The aim of the study was to identify the significance of MDM2 promoter SNP309 mutation and hematopoietic lineage cell-specific protein 1 (HS1) expression in the prognosis of CLL.
Forty-eight newly diagnosed Egyptian CLL patients were clinically evaluated and assessed for MDM2 promoter SNP309 mutation, HS1 expression, ZAP-70 expression, 17p13 deletion, and 13q14 deletion. Thirty-one patients received chemotherapy, and the type of response to chemotherapy was observed.
The results showed that MDM2 promoter SNP309 mutation was associated with cytogenetic abnormalities, the need to receive chemotherapy, and the response to fludarabine/cyclophosphamide in treated patients. HS1 expression was not associated with any of the studied CLL characteristics at diagnosis. Moreover, no association was found between HS1 expression and the need to receive chemotherapy during the study period. However, a significant association between HS1 expression and the response to fludarabine/cyclophosphamide was found.
The study concluded that, despite the opposing researchers’ reports, MDM2 promoter SNP309 mutation and HS1 expression are candidate prognostic markers for CLL patients awaiting a large-scale evaluation.