scholarly journals Assessment of microRNA expression in leukemic cells as predictors of sensitivity to purine nucleoside analogs, fludarabine and cladribine, in chronic lymphocytic leukemia patients

2019 ◽  
Vol Volume 11 ◽  
pp. 5021-5031
Author(s):  
Agnieszka Szymczyk ◽  
Sylwia Chocholska ◽  
Arkadiusz Macheta ◽  
Dariusz Szczepanek ◽  
Marek Hus ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nucleoside Analogs ◽  
Microrna Expression ◽  
Lymphocytic Leukemia ◽  
Purine Nucleoside ◽  
Leukemic Cells

scholarly journals Danazol induces apoptosis and cytotoxicity of leukemic cells alone and in combination with purine nucleoside analogs in chronic lymphocytic leukemia

2015 ◽  
Vol 95 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Monika Podhorecka ◽  
Arkadiusz Macheta ◽  
Sylwia Chocholska ◽  
Agnieszka Bojarska-Junak ◽  
Agnieszka Szymczyk ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Nucleoside Analogs ◽  
Lymphocytic Leukemia ◽  
Purine Nucleoside ◽  
Leukemic Cells

Valproate, a Histone Deacetylase Inhibitor, Enhances Purine Nucleoside Analogues Induced Apoptosis of B-Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4712-4712
Author(s):  
Amel B. Bouzar ◽  
Mathieu Boxus ◽  
Julien Defoiche ◽  
Hervé Balon Techn ◽  
Guy Berchem ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Histone Deacetylase ◽  
Nucleoside Analogs ◽  
Lymphocytic Leukemia ◽  
Purine Nucleoside ◽  
Deacetylase Inhibitor ◽  
Effective Doses ◽  
Therapeutic Protocols ◽  
Induced Apoptosis ◽  
Potential Use

Abstract Resistance to chemotherapy and drug toxicity are two major concerns of Chronic Lymphocytic Leukemia (B-CLL) treatment by Purine Nucleoside Analogs (PNA, i.e. fludarabine and cladribine). We hypothesized that targeting epigenetic changes might address these issues and evaluated the effect of the histone deacetylase (HDAC) inhibitor valproate (VPA) at a clinically relevant concentration. We show that VPA acts in a highly synergistic/additive manner with 9-ß-D-arabinosyl-2-fluoroadenine-5′-monophosphate (F-ara-AMP, fludarabine, 1μM) and 2-chloro-2′-deoxyadenosine (CdA, cladribine, 1μM) to induce apoptosis of CLL cells. VPA, but neither fludarabine nor cladribine, enhances the production of Reactive Oxygen Species (ROS) and inhibition of ROS with N-acetylcysteine decreases apoptosis of CLL cells. VPA-induced apoptosis is caspase-dependent and involves the extrinsic initiation pathway. VPA stimulates hyperphosphorylation of p42/p44 Erk as well as overexpression of Bax, cytochrome c and Fas. These observations support a potential use of VPA alone or in combination with nucleosidic analogs in CLL therapeutic protocols allowing a reduction of their effective doses or improving their efficacy in PNA-resistant patients.

scholarly journals APPLICATION OF NEW DRUGS IN CHRONIC LYMPHOCYTIC LEUKEMIA

2010 ◽  
Vol 2 (2) ◽  
pp. e2010011 ◽  
Author(s):  
Tadeusz Robak
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Chronic Lymphocytic Leukemia ◽  
Clinical Studies ◽  
Nucleoside Analogs ◽  
Lymphocytic Leukemia ◽  
New Drugs ◽  
Purine Nucleoside ◽  
Preclinical Studies ◽  
New Agents

Over the last few years, several new agents have been under evaluation in preclinical studies as well as in early clinical trials, and have shown promise in treating CLL. These treatments include new  monoclonal antibodies (mAbs), immunomodulating agents, novel purine nucleoside analogs, Bcl-2 inhibitors and other agents. The most promising are a new mAbs targeted CD20 molecule or CD23, anti-CD40 mAbs and anti-CD37 antibody. Oblimersen , flavopiridol, and lenalidomide are also being evaluated both in pre-clinical studies and in early clinical trials. However,  available therapies are only partially efficient and there is an obvious need to develop better strategies and new, more specific and active drugs

scholarly journals The pathological features of leukemic cells infiltrating the renal interstitium in chronic lymphocytic leukemia/small lymphocytic lymphoma from a large single Chinese center

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Hui Wang ◽  
Xiaojuan Yu ◽  
Xu Zhang ◽  
Suxia Wang ◽  
Minghui Zhao
Keyword(s):  
Electron Microscopy ◽  
Chronic Lymphocytic Leukemia ◽  
Renal Injury ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Cell Infiltration ◽  
Small Lymphocytic Lymphoma ◽  
Tubulointerstitial Injury ◽  
Renal Interstitium ◽  
Monoclonal Immunoglobulins

Abstract Background Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare in Asians, and patients with CLL/SLL seldomly undergo kidney biopsy. The histopathological features and clinical relevance of tubulointerstitial injury in CLL/SLL have not been extensively characterized. Hence, we attempted to describe the clinical characteristics, renal pathology and clinical outcome of a well-characterized population of CLL/SLL patients with CLL cell infiltration in the renal interstitium from a large single center in China. Methods Between January 1st, 2010 and September 31st, 2020, 31946renal biopsies were performed at Peking University First Hospital, and 10 CLL/SLL patients with CLL cell infiltration in the renal interstitium were included. Complete clinical data were collected from these 10 patients, and renal specimens were examined by routine light microscopy, immunofluorescence and electron microscopy. Results The extent of the infiltrating CLL cells in patients with CLL/SLL varied among different patients and ranged from 10 to 90% of kidney parenchyma. Six (60%) of 10 patients presented with an extent of infiltrating CLL cells ≥50%. Interestingly, we found that three patients (3/10, 30%) expressed monoclonal immunoglobulins in the infiltrating CLL cells, and special cytoplasmic crystalline structures were found in two of the three patients by electron microscopy for the first time. Severe renal insufficiency (Scr ≥200 μmol/L) was associated with ≥50% interstitial infiltration of CLL cells in the renal interstitium. Conclusions The current study confirmed that CLL cells infiltrating the renal interstitium can directly secrete monoclonal immunoglobulins, indicating that the interstitial infiltrating CLL cells possibly cause renal injury directly by secreting monoclonal immunoglobulins in situ. This finding may prove a new clue to elucidate the pathogenetic mechanism of renal injury involved with CLL/SLL.

scholarly journals Assessment of micro RNAs expression in leukemic cells as prognostic markers in chronic lymphocytic leukemia: micro RNAs can predict survival in a course of the disease

Oncotarget ◽  
2018 ◽  
Vol 9 (27) ◽  
pp. 19136-19146 ◽  
Author(s):  
Agnieszka Szymczyk ◽  
Sylwia Chocholska ◽  
Arkadiusz Macheta ◽  
Dariusz Szczepanek ◽  
Marek Hus ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Prognostic Markers ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Micro Rnas

scholarly journals Prognostic significance of immunoglobulin phenotype in B cell chronic lymphocytic leukemia

Blood ◽  
1985 ◽  
Vol 65 (2) ◽  
pp. 340-344 ◽  
Author(s):  
L Baldini ◽  
R Mozzana ◽  
A Cortelezzi ◽  
A Neri ◽  
F Radaelli ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Clinical Stage ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Clinical Prognosis ◽  
Delta Type ◽  
Cell Chronic Lymphocytic Leukemia

Abstract Seventy-six consecutive untreated patients with B cell chronic lymphocytic leukemia (B-CLL) and classified according to Binet's staging system were studied at the clinical presentation. Several immunologic parameters (number of total and T circulating lymphocytes and their surface membrane immunoglobulin [Smlg] phenotypes and levels of serum Ig) were evaluated with the aim of identifying a biologic marker of prognostic relevance. In this series of persons, Binet staging confirmed its usefulness as a prognostic index (P less than .001). With regard to Smlg, they were mu-type in 41 cases (53.9%), mu- type plus delta-type in 29 cases (38.2%), alpha-type in one case, and not detectable in five cases. No correlations were found between clinical stage and immunoglobulin phenotype, although all but one patient in stage C showed mu-type Smlg alone. On analyzing the survival curves of our patients according to different Smlg phenotypes, we found that patients with only mu-type Smlg had a poorer prognosis (P less than .05) than those with mu-type plus delta-type; this difference was even more significant (P less than .01) in patients in stage A, whereas there were no statistical differences in those in stages B and C. Because the appearance of surface heavy chain of delta-type could be an expression of cell maturation, these results suggest that in B-CLL the presence of phenotypically more mature leukemic cells may correlate with better clinical prognosis, particularly in the early phase of the disease.

scholarly journals Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL)

Blood ◽  
1978 ◽  
Vol 52 (5) ◽  
pp. 886-895 ◽  
Author(s):  
M Borgers ◽  
H Verhaegen ◽  
M De Brabander ◽  
J De Cree ◽  
W De Cock ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Healthy Subjects ◽  
Purine Nucleoside Phosphorylase ◽  
Peripheral Blood Lymphocytes ◽  
Lymphocytic Leukemia ◽  
Purine Nucleoside ◽  
Salvage Pathway ◽  
Purine Salvage ◽  
Nucleoside Phosphorylase ◽  
A Minor

Abstract Purine nucleoside phosphorylase (PNP), the enzyme schematically next to adenosine deaminase in the purine salvage pathway, has been demonstrated cytochemically in peripheral blood lymphocytes of healthy subjects and chronic lymphocytic leukemia (CLL) patients. The enzyme activity is confined to the cytosol. In healthy subjects the majority of lymphocytes are strongly reactive for PNP, whereas the rest are devoid of cytochemically demonstrable activity. The percentage of PNP- positive cells largely corresponds to the number of E rosette-forming cells and is inversely proportional to the number of Ig-bearing cells. In six of seven CLL patients studied only a minor percentage of the lymphocytes showed strong PNP activity, whereas the large majority (88%- -98%) possessed trace activity. Such patients have a high number of Ig- bearing cells and a low number of E rosette-forming cells. A different pattern of markers was found in the lymphocytes of the seventh CLL patient: 66% were strongly reactive for PNP, an important number formed E rosettes, and a minor percentage were Ig bearing. These data indicate that PNP can be useful as a “nonmembrane” marker in the differentiation of the B and T cell origin in CLL and deserves to be studied in other lymphoproliferative disorders.

Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2973-2979 ◽  
Author(s):  
Anne J. Novak ◽  
Richard J. Bram ◽  
Neil E. Kay ◽  
Diane F. Jelinek
Keyword(s):  
B Cells ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
B Lymphocyte ◽  
Leukemic Cell ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Aberrant Expression ◽  
B Lymphocyte Stimulator

B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5+ B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, we demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.

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