Bilateral exudative retinal detachment as a presenting sign of acute lymphoblastic leukemia
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Abstract:
Acute lymphoblastic leukemia (ALL) can present with various ocular complications but exudative retinal detachment is a rare complication. A 36-year-old healthy young adult male presented with gradual decrease in the vision in both eyes over nearly 2 weeks. His best-corrected visual acuities were 20/50 and 20/25 at distance and N12 and N10 at near in the right and left eyes, respectively. Fluorescein angiography and optical coherence topography indicated bilateral exudative retinal detachment. Systemic workup revealed a marked increase in the number of white blood cells with 30% blast cells and immunophenotyping revealed common acute lymphoblastic leukemia-associated antigen (CALLA) positive precursor B-cell lymphoblastic leukemia. Cerebrospinal fluid (CSF) tap was negative. The patient started systemic chemotherapy and steroids. Bilateral exudative retinal detachment may be a presenting sign of acute lymphoblastic leukemiaALL in an otherwise healthy young adult. Clinicians should be aware of the possibility of leukemia in such patients. A simple blood investigation such as complete blood profile confirms the diagnosis.Keywords:
Immunophenotyping
Dasatinib is an ABL1 tyrosine kinase inhibitor (TKI) with a short in vivo plasmatic half-life but with good efficiency, which is not fully understood. We investigated the possibility that circulating erythrocytes store and then provide dasatinib to target cells. In vitro coincubation of dasatinib-treated cells with naïve leukemic cells followed by analysis of kinase inhibition, apoptosis induction, fluorescent molecule exchanges, and dasatinib dosage were performed. Cells incubated with clinically relevant concentrations of dasatinib for a short time retained, after a washout procedure, an intracellular pool of dasatinib which was transferable to naïve BCR-ABL1 expressing cells and induced their apoptosis. This was verified in total blood where the huge cellular volume of erythrocytes constituted a large reservoir of dasatinib able to induce apoptosis in naïve BCR-ABL1 cell lines and primitive chronic myeloid leukemia (CML) CD34+ cells. This dasatinib transfer necessitated a contact between donor and acceptor cells. A component exchange occurred during this contact, carrying dasatinib and other TKIs such as nilotinib or the fluorescent sunitinib. An active pool of dasatinib could be buried inside the circulating erythrocytes, out of reach of detoxifying mechanisms, but still available for target cells and thus extending the acute effect of the plasmatic pool of the drug.
Chronic myelogenous leukemia
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Immunophenotyping
Cytometry
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Fifty-nine adult patients with acute leukemia were classified using a combination of the French-American-British (FAB) criteria and characterization by immunophenotyping using flow cytometric study. The authors identified 51 patients with acute myeloblastic leukemia and eight with acute lymphoblastic leukemia. This procedure permitted lineage assignment in leukemias that otherwise might have been unclassifiable. In addition, the authors demonstrated that the leukemic blasts of 29% of patients with myeloblastic disease exhibited one or more T-cell antigens on their surface. The use of immunophenotyping has greatly enhanced the authors' ability to correctly identify the lineage of acute leukemias. The data, however, must be interpreted with caution with respect to diagnosing acute mixed lineage leukemias and must be integrated with the morphologic and cytochemical evaluation of traditional classification schemes. The possible significance of T-cell markers in myeloblastic leukemia is discussed.
Immunophenotyping
Acute myeloblastic leukemia
Lineage (genetic)
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Immunophenotyping
Lineage (genetic)
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Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. Dasatinib is commonly used for the treatment of acute lymphoblastic and chronic myelogenous leukemia. Previous clinical studies in melanoma returned inconclusive results and suggested that patients respond highly heterogeneously to dasatinib as single agent or in combination with standard-of-care chemotherapeutic dacarbazine. Reliable biomarkers to predict dasatinib responsiveness in melanoma have not yet been developed. Here, we collected comprehensive in vitro data from experimentally well-controlled conditions to study the effect of dasatinib, alone and in combination with dacarbazine, on cell proliferation and cell survival. Sixteen treatment conditions, covering therapeutically relevant concentrations ranges of both drugs, were tested in 12 melanoma cell lines with diverse mutational backgrounds. Melanoma cell lines responded heterogeneously and, importantly, dasatinib and dacarbazine did not synergize in suppressing proliferation or inducing cell death. Since dasatinib is a promiscuous kinase inhibitor, possibly affecting multiple disease-relevant pathways, we also determined if basal phospho-protein amounts and treatment-induced changes in phospho-protein levels are indicative of dasatinib responsiveness. We found that treatment-induced de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma. Loss of p53 phosphorylation might be an interesting candidate for a kinetic marker of dasatinib responsiveness in melanoma, pending more comprehensive validation in future studies.
Dacarbazine
Chronic myelogenous leukemia
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Objective To investigate the immunophenotyping characteristics of children with acute leukemia,and to comprehend the regular patterns of CD antigens in children with acute leukemia.Methods The 3-color flow cytometry and CD45/Side Scatter(SSC) gating were used to analyze the surface and cytoplasmic(Cy) antigens expressed in 156 successive cases of children with acute leukemia.Results Based on the diagnostic criterions proposed by European Group for the Immunological Characterization fo Leukemia(EGIL),4 categories were divided into:the undifferentiated type accounted for 0.7%,acute lymphocytic leukemia(ALL) 69.2%,acute myeloid leukemia(AML) 25%,and mixed lineage AL 5.1%.Of 108 patients with ALL,90.7% were classified as B lineage ALL and 9.3% as T lineage ALL.CD10,CD19 and CD20 antigens were highly expressed in B-ALL,with positive percentage of 83.5%,98.9%,21.6%.And CD13,CD33,CD117 antigens were highly expressed in AML,with positive percentage of 94.8%,94.8%,67.6%,86.5%.CD34 and HLADR were lower in patients with AML-M3 than other types of AML,the differences were significant(P0.05).Conclusion Immunophenotyping with flow cytometry is of great significance in children with acute leukemia,and is a useful assistant tool to morphology.
Immunophenotyping
Cytometry
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The article contains results of meta-analysis of experience in use of second-generation tyrosine kinase inhibitors – dasatinib. The results of clinical trials dasatinib therapy in chronic myelogenous leukemia imatinib-resistant or intolerant patients are presented. The dasatinib and imatinib comparative analysis in first-line therapy in newly diagnosed chronic myelogenous leukemia patients are demonstrated. The range and frequency of dasatinib therapy adverse events are analyzed. Toxicities management recommendations are listed. Perspectives of dasatinib therapy cessation in patients with long lasting deep molecular responses – treatment free chronic myelogenous leukemia remissions are descripted. Also, there is an information about dasatinib usage in treatment of Philadelphia-positive acute lymphoblastic leukemia.
Chronic myelogenous leukemia
Imatinib Mesylate
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BACKGROUND: The identification of aberrant phenotypes in acute leukemia is crucial for treatment monitoring and minimal residual disease analysis. Flowcytometric immunophenotyping in acute leukemia is an important tool for the detection of these aberrancies. There is wide variation in the incidence of aberrant antigens in acute leukemia in different studies and its correlation with prognostic markers.AIMS AND OBJECTIVES: The aim and objective of this study is to assess the frequency of aberrant markers in acute leukemia and determine any association with hematological parameters.MATERIALS AND METHODS: A total of 150 newly diagnosed cases of acute leukemia during the period January 2018–December 2020 were included. The flowcytometric immunophenotyping of all the above cases was done using BD FACS Canto II.RESULTS: Out of the total 150 cases of acute leukemia, 56.7% expressed aberrant phenotype. The proportional frequency of aberrant antigen expression in B-acute lymphoid leukemia (ALL), T-ALL and acute myeloid leukemia (AML) was 56.6%, 50%, and 58.5%, respectively. CD13, CD13, and CD7 were the most common aberrancies in B-ALL, T-ALL, and AML, respectively. Aberrant myeloid phenotype in B-ALL was associated with lower mean total leukocyte count (TLC) and blast percentage in peripheral blood as compared to the B-ALL with conventional phenotypes. Aberrant lymphoid phenotype in AML was associated with a higher TLC and greater blast percentage in peripheral blood than the AML with conventional phenotypes.CONCLUSION: Aberrant lymphoid phenotype in AML is associated with unfavorable hematological features. However, aberrant myeloid phenotype in B-ALL is not associated with adverse features.
Immunophenotyping
Minimal Residual Disease
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Objective:To investigate the expression of CD 56 on acute leukemia and its clinical manifestation.Methods:Immunophenotype of 92 cases with acute leukemia was measured by flow cytometry,the morphology,immunophenotype and clinic of CD 56 positive patients was analyzed.Results:15/92(16.3%)cases with acute leukemia expressed CD 56 ,one patient has been tesified to be myeloid/NK cell precursor acute leukemia,one patient has been testified to be blastic NK cell leukemia,one patient has been testified to be NK like T cell lymphoma/leukemia,12 patients are like to be acute myeloid leukemia with NK antigen expression or myeloid/NK cell acute leukemia.Conclusion:CD 56 positive acute leukemia is heterogeneous,its morphology,immunophenotype and clinical manifestation is different,they were associated with M 2?M 5?L 2;they had more infiltration out marrow and prognosis was poor.
Immunophenotyping
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Introduction: Dasatinib is a novel tyrosine kinase inhibitor with activity against the Src family kinases. The Src pathway is active in breast cancer and has been shown to promote cell proliferation, invasiveness, and metastases. Preclinical data support the use of dasatinib to inhibit breast cancer cell growth, modulate hormone and EGFR signaling, and alter cell migration. Areas covered: This article details the preclinical data supporting dasatinib's use in breast cancer treatment. Additionally, Phase I/II studies that have tested dasatinib as a single agent and in combination with chemotherapy and antihormonal agents are discussed. Expert opinion: Phase I/II studies to date have shown only limited responses to dasatinib among breast cancer patients. Dasatinib has no current role in the treatment of breast cancer, and its future is uncertain. No specific subset of patients has been identified which preferentially responds to treatment. Studies are under way to identify specific molecular markers that might predict response to dasatinib.
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