scholarly journals Pseudohyperkalemia in Patients with Chronic Lymphocytic Leukemia

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Stephen I. Rifkin
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
Mechanical Stress ◽  
White Blood Cell ◽  
Whole Blood ◽  
Correct Diagnosis ◽  
Plasma Potassium ◽  
Lymphocytic Leukemia ◽  
Blood Potassium

Pseudohyperkalemia occurs occasionally in patients with extreme leukocytosis. Increased white blood cell fragility coupled with mechanical stress is felt to be causal. Serum and plasma potassium levels have been both associated with pseudohyperkalemia. Whole blood potassium determination will usually verify the correct diagnosis. It is important to diagnose this condition early so that patients are not inappropriately treated. Two patients with chronic lymphocytic leukemia and extreme leukocytosis are presented, one with pseudohyperkalemia and one with probable pseudohyperkalemia, and diagnostic considerations are discussed

scholarly journals High Aurora Kinase and Low Dido Levels Characterizes a Sub-Group of Chronic Lymphocytic Leukemia with Chromosomal Gains and High White Blood Cell Counts: Potential Inter-Regulatory Role of E2F1 and Mir-17-92 Cluster

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2029-2029
Author(s):  
Felipe C Souza ◽  
Josiane L Schiavinato ◽  
Antonio R. Lucena-Araujo ◽  
Fabio M Oliveira ◽  
Amelia G Araújo ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
White Blood Cell ◽  
Chromosomal Instability ◽  
Regulatory Mechanism ◽  
Lymphocytic Leukemia ◽  
Transcript Levels ◽  
Expression Levels

Abstract During cell cycle division Aurora kinases (AURKA and AURKB) participate in the formation and control of mitotic spindle fibers, while, protein isoforms (DIDO1, DIDO2 and DIDO3), derived by alternative splicing of the DIDO gene, assist at the junction of microtubules to kinetochores. Thus, both are relevant to cell cycle maintenance. Interestingly, overexpression (or gain of function) of AURKs or low expression (or loss of function of DIDO) are both associated with centrosomal amplification and chromosomal instability (CIN), leading to aneuploidy. Among hematological diseases with CIN records, chronic lymphocytic leukemia (CLL) can display centrosome amplification and changes in AURKs expression levels leading to aneuploidy. The Despite this, there are no studies evaluating the potential association of these genes with CIN in CLL. By evaluating their gene expression levels in CLL samples from patients with or without chromosomal aberrations, we show that increased levels of AURKA and AURKB and, conversely, reduced levels of DIDO variants, are both significantly associated with chromosomal gains and with increased white blood cell (WBC) counts. Clearly, CLL samples without any cytogenetic abnormality had expression levels similar to samples mostly harboring non-numerical aberrations. The finding that the expression levels of AURKs and DIDO variants are completely opposed, showing a discrete inter-related pattern, led us to investigate the potential regulatory mechanism behind this. Given that other have previously shown that the oncogenic miR-17-92 cluster is significantly upregulated in purified CLL patient cells expressing unmutated IGHV genes (as compared to mutated patient cells), and that miR-17 is expressed at significantly higher levels in unmutated or ZAP-70 high cases (bad prognostic cases generally associated with chromosomal instability), we investigated the potential negative regulation of DIDO variants by microRNAs from this cluster. In addition, based on the already described regulatory mechanism by which AURKA overexpression induces the E2F1-mediated transcription upregulation of the miR-17-92 cluster (with an observed expression correlation of both proteins in cancer specimens); we decided to investigate this regulatory axis in CLL. Notably, we found that all DIDO variants are predicted to be heavily targeted by several miRs of this oncogenic cluster. We show that CLL samples with low DIDO expression, in addition to the already mentioned AURK high levels, displayed significant higher levels of the transcription factor E2F1 and of its transcriptional target, the miR-17-92 primary transcript (MIR17HG). Moreover, by using the NTERA-2 cell line as a model, we show that siRNA knockdown of AURKA (at the transcript and protein level, as confirmed by qPCR and western blot) is accompanied by a striking significant reduction of E2F1 and also of MIR17HG. Furthermore, transfection of NTERA-2 cells with synthetic mimics of the miR-17~92 cluster (namely, miR-19a, miR-20a and miR-92a) results in a clear and significant reduction in the transcript levels of all DIDO variants. Finally, specific siRNA inhibition of the DIDO3 variant (but not the others) led to a significant reduction in the transcript levels of all DIDO variants, indicating an additional mechanism contributing to the downregulation of DIDO transcripts. Altogether, our results demonstrate the existence of a potential interconnected regulatory mechanism between AURK and DIDO, associated with CIN and higher WBC counts in CLL. More importantly, the high expression levels of AURKs and the associated low levels of DIDO variants are specifically associated with cytogenetic abnormalities presenting chromosomal gains, highlighting the specific cellular mechanism underlying the CIN observed in this distinct CLL group. Given the central role of CIN in cancer genesis and progression, these findings will likely have an important impact on prognosis or treatment of CLL. Funded by: FAPESP, CNPq and CAPES. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk Factors of White Blood Cell Progression Among Patients With Chronic Lymphocytic Leukemia at Felege Hiwot Referral Hospital, Bahir Dar, Ethiopia

2022 ◽  
Vol 21 ◽  
pp. 117693512110699
Author(s):  
Gedam Derbew Addisia ◽  
Awoke Seyoum Tegegne ◽  
Denekew Bitew Belay ◽  
Mitiku Wale Muluneh ◽  
Mahider Abere Kassaw
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
White Blood Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Lymphocytic Leukemia ◽  
Bahir Dar ◽  
Felege Hiwot Referral Hospital ◽  
Wbc Count

Background: Leukemia is a type of cancers that start in the bone marrow and produce a serious number of abnormal white blood cells. Bleeding and bruising problems, fatigue, fever, and an increased risk of infection are among symptoms of the disease. The main objective of this study is to identify the determinant of the progression rate of white blood cells among patients with chronic lymphocytic leukemia at Felege Hiwot Referral Hospital (FHRH), Bahir Dar, Ethiopia. Methods: A retrospective study design was conducted on 312 patients with chronic lymphocytic leukemia at FHRH, Bahir Dar, Ethiopia under treatment from 1 January 2017 to 31 December 2019. A linear mixed-effects model was considered for the progression of the white blood cell data. Results: The estimated coefficient of the fixed effect intercept was 84.68, indicating that the average white blood cell (WBC) count of the patients was 84.68 at baseline time by excluding all covariates in the model ( P-value <.001). Male sex ( β = 2.92, 95% confidence interval [CI] 0.58, 0.5.25), age ( β = .17, 95% CI 0.08, 0.28), widowed/divorced marital status ( β = 3.30, 95% CI 0.03, 6.57), medium chronic lymphocytic leukemia (CLL) stage ( β = −4.34, 95% CI −6.57, −2.68), high CLL stage ( β = −2.76, 95% CI −4.86, −0.67), hemoglobin ( β = .15, 95% CI 0.07, 0.22), platelet ( β = .09, 95% CI 0.02, 0.17), lymphocytes ( β = .16, 95% CI 0.03, 0.29), red blood cell (RBC) ( β = .17, 95% CI 0.09, 0.25), and follow-up time ( β = .27, 95% CI 0.19, 0.36) were significantly associated with the average WBC count of chronic lymphocytic leukemia patients. Conclusions: The finding showed that age, sex, lymphocytic, stage of chronic lymphocytic leukemia, marital status, platelet, hemoglobin, RBC, and follow-up time were significantly associated with the average WBC count of chronic lymphocytic leukemia patients. Therefore, health care providers should give due attention and prioritize those identified factors and give frequent counseling about improving the health of chronic lymphocytic leukemia patients.

The effects of sildenafil citrate on malignant B-cells in patients with chronic lymphocytic leukemia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7076-7076
Author(s):  
B. A. McGregor ◽  
A. Gorrebeeck ◽  
E. Struble ◽  
A. Harroff
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
Cell Count ◽  
White Blood Cell Count ◽  
White Blood Cell ◽  
Lymphocytic Leukemia ◽  
Western Hemisphere ◽  
Blood Cell Count ◽  
Apoptosis Rate

7076 Background: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western Hemisphere, with over 10,000 cases diagnosed annually in the United States. It is characterized by progressive accumulation of functionally incompetent long-lived lymphocytes, shown to be secondary to a defect in programmed cell death or apoptosis. The phosphodiesterase inhibitor sildenafil induces capsase dependent apoptosis of malignant B lymphocytes in vitro. This study will test the hypothesis that sildenafil reduces the expression of BCL-2 and increases the spontaneous apoptosis rate of malignant B-cells in patients with CLL. Methods: Thirteen patients with Rai Stage 0 CLL were enrolled. Nine of the patients were aged sixty-five years or older and received sildenafil 25 mg weekly; four patients were under the age of sixty-five and received sildenafil 25 mg weekly. All patients took the medication for a total of three months. Lymphocyte counts, BCL-2 expression, caspase 3 activity, and apoptosis rate were monitored on enrollment and monthly for duration of the study. Results: The median age of patients enrolled in the study was 74 with a median white blood cell count of 18 x103/mL. Twelve of the 13 patients completed three months of therapy. While one patient withdrew due to blehparitis, not felt to be a side effect of sildenafil, all other patients tolerated the medication well without any adverse effects. There was no significant decrease in white blood cell count or Bcl-2 expression; capsase 3 activity and apoptosis rates remained undetectable on presentation and throughout treatment. Conclusions: At a dose of 25 to 50 mg weekly, sildenafil does not appear to have any effects on the malignant B cells in CLL. While this dose may not produce a measurable clinical or cellular response, higher doses may still have an effect on the malignant B cells of CLL. The dose of sildenafil was based on a case series of patients with Viagra who had decreases in IgM levels while taking sildenafil 25–50 mg weekly. Subsequent studies in have shown a greater reduction in IgM in patients taking sildenafil 100 mg daily and patients did not report any significant side effects. A follow-up study using sildenafil 100 mg daily is warranted. No significant financial relationships to disclose.

scholarly journals Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia

Oncotarget ◽  
2016 ◽  
Vol 7 (22) ◽  
pp. 32846-32853 ◽  
Author(s):  
Monika Podhorecka ◽  
Dorota Halicka ◽  
Agnieszka Szymczyk ◽  
Arkadiusz Macheta ◽  
Sylwia Chocholska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Blood Cell ◽  
Prognostic Marker ◽  
Red Blood Cell ◽  
Lymphocytic Leukemia ◽  
Cell Distribution ◽  
Distribution Width ◽  
Red Blood Cell Distribution

Inhibition of Bortezomib-Induced Apoptosis in Chronic Lymphocytic Leukemia by Red Blood Cell Uptake.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5027-5027
Author(s):  
Luise M.C. Wheat ◽  
Susan L. Kohlhaas ◽  
Johan Monbaliu ◽  
Roland De Coster ◽  
Aneela Majid ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Whole Blood ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Cell Uptake ◽  
Reversible Inhibitor ◽  
Apoptotic Pathway ◽  
Mutational Status ◽  
Induced Apoptosis

Abstract Bortezomib (PS-341/Velcade™) is a reversible inhibitor of the proteasome that has shown promising activity in clinical trials in several malignancies including multiple myeloma, mantle cell lymphoma and follicular lymphoma, including those with refractory disease. However, results have been less encouraging in chronic lymphocytic leukemia (CLL) and we have, therefore, sought to determine the barriers to effective therapy with bortezomib in this disease. Patients with CLL were eligible but were required to have received no therapy in the six months prior to the study. In a panel of 26 patients with CLL, both purified mononuclear cells and whole blood were tested for their apoptotic response to bortezomib (1–100 nM) up to 24 h by flow cytometry and western blotting. In all cases, purified CLL cells were sensitive to bortezomib-induced apoptosis in a concentration and time-dependent fashion, irrespective of stage of disease, resistance to prior therapy, IGHV mutational status or the presence of TP53 mutations. Apoptosis was induced at low (&gt;10 nM) nanomolar concentrations of bortezomib by activation of the intrinsic apoptotic pathway. Bortezomib-induced apoptosis correlated with levels of ubiquitination, Bax activation, and caspase cleavage. Apoptosis of CLL cells was obtained at drug levels readily obtained in vivo using currently-used dosing protocols. However, in vitro, it was necessary to maintain these concentrations for 16–24 hours to obtain maximal apoptosis. Apoptosis measured in a whole blood apoptosis assay was markedly less than in isolated lymphocytes at comparable time points and concentrations. Activity of bortezomib in purified cells was not diminished by addition of exogenous plasma but was abrogated by addition of autologous red blood cells (RBC), suggesting preferential active uptake of the drug by these cells. These data were confirmed in animal models showing preferential distribution of bortezomib to the RBC fraction. RBC uptake may therefore account for the low serum levels of bortezomib attained in vivo during terminal half-life and thus the lack of activity against cells in the peripheral blood. Together with pharmacokinetic and in vivo data, these studies suggest that different dosing schedules of bortezomib other than bolus injections may be more effective in patients with CLL.

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