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  • br Discussion CML was the first malignancy to

    2019-05-04


    Discussion CML was the first malignancy to be linked to a clear genetic abnormality, the Philadelphia chromosome. This chromosomal abnormality is so named because of the city in which it was first discovered and described in 1960 by Peter Nowell and David Hungerford [1]. The fusion protein results in increased activity of a tyrosine kinase and several other signal transduction pathways with deregulation of the normal control mechanisms of granulopoiesis [2]. In most published series of consecutive patients diagnosed with CML the total leukocyte counts are elevated [3]. In one recent series [4], 245 patients were analyzed and 178 of these (72.6%) were in Chronic Phase. The mean total leukocyte count was 168 × 109/L (range:35–959). In 1972 Canellos and Whang-Peng [5] reported on a 43-year-old male with a leukocyte count of 8800/cmm but 6% metamyelocytes and 7% myelocytes. Examination was normal. The Ph was detected in 22% of the metaphases and the patient remained asymptomatic for five years without treatment before developing a blast crisis. A second case was reported more recently by Hudnall and coworkers from the University of Texas, Galveston. [6] Their case was complicated by the simultaneous presentation of Hodgkin lymphoma, Stage III, successfully treated. The total leukocyte count remained normal for 15 months after recognition of the BCR-ABL transcript.
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    Letter to editor Despite recent progress in approach of malignant haemopathies, their prognosis frequently remains poor due to the difficulty to achieve complete remission (CR) and to the high risk of relapse. Immunotherapy could thus be of great interest in this setting. Specific immunotherapy is mainly challenged by the defect of expression of major histocompatibility complex (MHC) molecules frequently observed in cancer cells, together with the progressive selection of cancer clones that have lost their MHC molecules and thus escape from immune control by specific T-lymphocytes. In sharp contrast, natural killer (NK) purchase Lomustine are able to kill target cells in a MHC-independent way, i.e. these cells “sense” the absence or abnormal expression of MHC molecules to express their cytolytic capacities, provided that tumor cells express ligands for NK activating receptors (for review, [3]). Among activating NK molecules, the so-called natural cytotoxicity receptors (NCRs) NKp30/NCR3, NKp44/NCR2 and NKp46/NCR1, together with NKG2D and 2B4/CD244 play a pivotal role in NK cytotoxicity and probably in their anti-leukemia effect [4]. Since the expression of activating molecules is down-regulated in myeloid malignancies, we hypothesized that demethylating agents such as 5-azacytidine [5], used in the treatment of RAEB and AML with <30% blast infiltration in bone marrow, could contribute to the restoration of a normal phenotype of NK. The work described has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki). Blood samples were obtained, before any treatment, from 6 patients with RAEB II after informed consent. The analysis of PB was done less than 4h after blood sampling, on whole blood after red blood cell lysis (Q-PrepR lysing kit, Beckman-Coulter, Villepinte, France). The NK cell population was defined as CD3-/CD56+. The following mAbs were all obtained from Beckman-Coulter: anti-CD3FITC (UCHT1), anti-CD56PC5 (N901-NKH1), anti-NCR1/NKp46PE, anti-NCR2/NKp44PE, anti-NCR3/NKp30PE, anti-NKG2DPE, anti-CD244(2B4,p38)PE. Triple staining was performed using CD3FITC/CD56PC5 in addition with anti-NCR1/NKp46PE, anti-NCR2/NKp44PE, anti-NCR3/NKp30PE. For cell surface staining, cells (5×105) were incubated for 20min at 4°C with 10μL of the corresponding antibodies for 100μL of cell preparation. Flow cytometry was performed on an Epics XLR flow cytometer (Beckman-Coulter). The results are expressed as follows; percentages correspond to (% positive cells – % isotype control), while the mean fluorescent intensities (MFI) correspond to the ratio (MFI positive cells / MFI isotype control). Statistical analysis was performed using the SPSS software (SPSS User׳s Guide. SPSS Inc, 1993).