ABSTRACT
A 10-yr-old HbE/Beta thalassemia child who developed subacute to chronic occipitotemporal hemorrhagic infarct with smaller chronic infarct with gliotic changes in the left frontal periventricular white matter. Genetic tests showed that patient was positive for HbE and IVS1-5 mutation and was negative for thrombogenic mutations. Hemorrhagic infarct was confirmed by magnetic resonance imaging study. Antigenic levels of Protein C and Protein S were low. Based on these outcomes, it was concluded that Protein C and Protein S deficiency were the causative factor for developing hemorrhagic infarct in the HbE/ Beta thalassemia patient.
Subject(s)
Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/etiology , Cerebral Infarction/diagnosis , Cerebral Infarction/etiology , Child , Humans , Magnetic Resonance Imaging , Male , Protein C Deficiency/complications , Protein C Deficiency/diagnosis , Protein S Deficiency/complications , Protein S Deficiency/diagnosis , beta-Thalassemia/complicationsABSTRACT
Background & objectives: Recurrent balanced translocations are generally recognized to be a major parameter for prognostication in acute myeloid leukaemia (AML). The chromosomal translocation t(15;17) results in PML/RARα fusion gene, t(8;21) results in AML1/ETO fusion gene and Inv 16 generates CBFβ/MYH11 fusion gene. Patients with these mutations have a good prognosis unlike abnormalities in chromosome 5 or 7 or FLT3 genes. Therefore, we screened the AmL patients for known specific genetic abnormalities that could lead to more definitive prognoses. Methods: A total of 113 AML patients were evaluated at diagnosis based on routine morphology and cytochemistry and classified according to the WHO criteria. The distribution of AML subtypes was M1(1), M2(32), M3(57), M4(14), M5(1), M6(1) and seven cases where morphological subtype could not be classified. RT-PCR was performed to identify PML/RARα, AML1/ETO, CBFβ/MYH11 and FLT3 internal tandem duplication (ITD). Results: Of the 57 patients with M3 subtype, 55 had the PML-RARα fusion transcript. The prevalence of bcr3 (short isoform) was higher (62%) than that of bcr1 (long isoform) (38%) and no correlation was found with age, sex or white blood cell count. FLT3 internal tandem duplication (ITD) mutations were more frequent in patients with APL than in other AML subtypes (17.5 vs. 8.9%), the frequency greater in patients with bcr3 isoform (70%) than in those with in bcr1 isoform (30%). Patients with FLT3/ITD mutations had a significantly higher median white cell count than those without these mutations (55 x 109/l vs. 6.3 x 109/l; P<0.001). More patients with FLT3/ITD mutations died early (53%) than those without these mutations (16%) (P<0.01). AML1-ETO fusion transcript was detected in 16 of 56 patients with no correlation with clinical or haematological parameters. Interpretation & conclusion: The results of the present study showed presence of bcr3 (short isoform) higher than bcr1 (long isoform). FLT3 internal tandem duplication (ITD) mutation was predominant in acute promyelocytic leukaemia patients with bcr3 isoform. Thus, patients with APL who have FLT3 mutation appear to have a poorer prognosis. Therefore, rapid identification of specific translocations at diagnosis is important for prognostic purposes and their detection should be incorporated into routine assessment.
Subject(s)
Adolescent , Adult , Child , Female , Gene Duplication , Genetic Predisposition to Disease/epidemiology , Humans , India/epidemiology , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged , Oncogene Proteins, Fusion/genetics , Prevalence , Prognosis , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors , Translocation, Genetic , Young Adult , fms-Like Tyrosine Kinase 3/geneticsABSTRACT
Translocation (8;21) is associated with few typical morphological features and favorable prognosis. All patients of AML and MDS with increased blasts (N = 35) according to FAB criteria, presenting (between Jan 2004 to June 2005) to the Department of Hematology, AIIMS were studied. RT-PCR was done for the AML1-ETO fusion transcript in all cases. Overall incidence of AML1-ETO was 28.57% and no correlation was found between AML1-ETO positivity and clinical or hematological parameters except for a direct correlation with absolute blast count (ABC) (a lower ABC in the AML1-ETO positive cases). Interestingly, 1/3 MDS cases were positive for the same fusion transcript and thus, it appears worthwhile to look for AML1-ETO in all cases of MDS with increased blasts. Objective morphological evaluation using a scoring system based on morphological features was not helpful in predicting positivity for AML1-ETO. The effect of this translocation on long-term survival could not be determined by the present study.