ABSTRACT
In chronic myeloid leukemia (CML) two main types of messenger RNA (e14a2 and e13a2) can be produced by BCR-ABL1 gene rearrangement. Due to conflicting results, the clinical value of these transcripts remains controversial. The aim of this study was to identify associations of e14a2 and e13a2 transcripts with laboratory variables and also the response to treatment. This study included 203 adult patients with CML treated with Imatinib as first-line drug in a reference hematology center in Northeast Brazil. Clinical and laboratory data were obtained after informed consent. Samples were collected for RNA extraction and analyzed by reverse transcription-polymerase chain reaction (PCR), according to the international protocol BIOMED-1. The LeukemiaNet 2013 criteria were used to establish the molecular response. The frequency distribution of the BCR-ABL1 transcripts was e14a2 (64%), e13a2 (34%), and double positives (2%). The results showed a statistically significant association of the e14a2 transcript type with thrombocytosis (P = 0.0005) and the e13a2 with higher leukocyte count (P = 0.0491). In a subgroup of 44 patients, the molecular response to treatment with Imatinib was assessed by quantitative PCR at 3 months (BCR-ABL1 ≤ 10%), 6 months (BCR-ABL1 ≤ 1%), or 12 months (BCR-ABL1 ≤ 0.1%). Although patients with the transcript e14a2 showed higher frequency of good responses than patients with the transcript e13a2, this difference was not statistically significant. In agreement with published data, our results showed association of the BCR-ABL1 transcript e14a2 with thrombocytosis and the BCR-ABL1 transcript e13a2 with higher leukocytosis in patients with chronic myeloid leukemia.
Subject(s)
Biomarkers, Tumor/genetics , Fusion Proteins, bcr-abl/genetics , Leukemia, Myeloid, Chronic-Phase/genetics , RNA, Messenger/genetics , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/metabolism , Female , Fusion Proteins, bcr-abl/metabolism , Humans , Imatinib Mesylate/therapeutic use , Leukemia, Myeloid, Chronic-Phase/blood , Leukemia, Myeloid, Chronic-Phase/drug therapy , Leukocyte Count , Male , Middle Aged , Platelet Count , RNA, Messenger/metabolismABSTRACT
Acute promyelocytic leukemia (APL) is characterized by the presence of rearrangements involving the retinoic acid receptor alpha (RARalpha) gene and a variable incidence in different populations. The hybrid gene PML-RARalpha, present in 98% of cases, encodes a fusion protein essential to the pathogenesis of the disease. Depending of the PML's gene breakpoint in chromosome 15, the transcript subtypes bcr1, bcr2 and bcr3 may be formed. The correlation between these transcript subtypes and clinical parameters is still controversial. The objective of this study was to determine the frequencies of the PML-RARalpha transcripts and subtypes in a series of 32 APL patients from Northeast Brazil and to evaluate the association of these subtypes to different parameters. The method used was RT-PCR. The frequency of our APL cases is approximately 28% of the acute leukemias. The results showed the presence of PML-RARalpha isoform in all patients and a higher frequency of the bcr1/2 subtype. No significant statistical association was found between molecular subtypes and age, sex, French-American-British (FAB) classification, leukocyte and platelet count, hemoglobin level or coagulation tests. In conclusion, these data suggest similar molecular and biological features for our APL patients at diagnosis in comparison with those reported in current scientific literature.
Subject(s)
Leukemia, Promyelocytic, Acute/genetics , Neoplasm Proteins/genetics , Oncogene Proteins, Fusion/genetics , Adolescent , Adult , Brazil , Child , Female , Hemoglobins/metabolism , Humans , Leukocyte Count , Male , Middle Aged , Neoplasm Proteins/blood , Oncogene Proteins, Fusion/blood , Platelet Count , Protein Isoforms/blood , Protein Isoforms/genetics , Proto-Oncogene Proteins c-bcr/geneticsABSTRACT
The distribution of lymphocyte subsets in blood, thymus, spleen, mesenteric lymph nodes, Peyer's patches and bone marrow was evaluated in an experimental model of secondary hemochromatosis in rats. The values of CD2, CD4, CD8, B and NK cells in these different lymphoid compartments did not differ between the control group and the experimental group. These results suggest that the abnormalities of lymphocyte subsets previously reported in patients with secondary hemochromatosis may be due to factors other than iron overload.
Subject(s)
Hemochromatosis/immunology , Lymphocyte Subsets/cytology , Animals , B-Lymphocytes/cytology , Bone Marrow Cells , CD2 Antigens/analysis , CD4 Antigens/analysis , CD8 Antigens/analysis , Hemochromatosis/blood , Killer Cells, Natural/cytology , Lymph Nodes/cytology , Lymphocyte Count , Lymphocyte Subsets/immunology , Male , Peyer's Patches/cytology , Rats , Rats, Wistar , Spleen/cytology , Thymus Gland/cytologySubject(s)
Infant, Newborn, Diseases/nursing , Tetanus/nursing , Humans , Infant, Newborn , Prognosis , Tetanus/diagnosis , Tetanus/drug therapyABSTRACT
A previously healthy girl, without heart disease, who ingested 2400 mg of verapamil developed hypotension, trifasicular block pattern, mental confusion, mild metabolic acidosis, and hyperglycemia. She recovered with symptomatic and supportive therapy. A discussion is presented about the action mechanism of the drug.
