Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Pseudotumour cerebri in acute promyelocytic leukemia on treatment with all-trans-retinoic acid (ATRA) - an experience from a tertiary care centre.

Acute promyelocytic leukemia (APML) is considered to be sensitive to all-trans-retinoic acid (ATRA) which acts as a differentiating agent. ATRA is considered to be a well-tolerated agent and is known to achieve complete remission in acute promyelocytic leukemia. However, a few cases on long term all-trans-retinoic acid (ATRA) use can develop pseudotumor cerebri. Out of 32 patients with APML who were treated in our Centre over a 4-year-period, we encountered 6 patients who developed ATRA-related pseudotumor cerebri while on maintenance treatment. The patients ranged from 12 to 40 years of age. 3 patients complained of unbearable headache, 2 of diplopia and 1 of gross reduction in visual acuity. CT scans and MRI did not reveal any intracranial lesions. Cerebrospinal fluid (CSF) examination was normal with CSF manometry revealing a high CSF pressure (average of 345mmH2O). Fundoscopy revealed papilledema in 5 patients and optic atrophy in 1 patient. The patients were successfully managed with decrease dose/discontinuation of ATRA, use of acetazolamide, corticosteroids and therapeutic CSF drainage.

Role of low dose cytarabine in elderly patients with acute myeloid leukemia: An experience.

PURPOSE: To highlight the acceptable results seen after use of low dose cytarabine in elderly patients of acute myeloid leukemia (AML) with comorbidities. MATERIALS AND METHODS: This was a prospective study carried on 30 newly diagnosed patients of AML over 60 years of age who were unfit for standard treatment regimens. We did not use azacytidine and decitabine in our patients because these therapeutic modalities being extremely costly and our patient affordability being poor. After taking patient consent and institutional ethical clearance these patients were treated with 20 mg/m(2) cytarabine subcutaneously in two divided doses 12 h apart for 4 days every week for 4 weeks which constituted a cycle before disease, re-assessment was done. A repeat cycle was administered where ever needed and after attainment of remission, we continued low dose cytarabine for 2 days/week as maintenance after complete or partial response was documented. RESULTS: In our study, we found that around 20% of patients achieved complete remission and 30% partial remission. The remission rates were definitely influenced by counts at presentation, performance at presentation, comorbidities, underlying myelodysplastic syndrome and baseline cytogenetics. CONCLUSION: Low dose cytarabine is effective treatment option for elderly patients with AML when standard treatment options are not warranted.

Pure Erythroleukemia (Variant Acute Myeloid Leukemia-vAML-M6) with Deletion of Chromosome 20, Mainly Presenting as Late Erythroblasts, a Unique Case Report with Review of Literature.

Acute erythroleukemia is characterized by a predominant immature erythroid population and accounts for approximately 2-5 % of all cases of acute leukemia. Two subtypes are recognized based on the presence or absence of a significant myeloid component: erythroleukemia and pure erythroid leukemia. Erythroleukemia is predominantly a disease of adults, while pure erythroid leukemia can be seen in any age including children. Here is a case of pure erythroleukemia presenting mainly as late erythroblasts which was diagnosed on bone marrow examination, cytochemistry and was confirmed on immunophenotyping. Possibly this is the only case so for demonstrating deletion of long arm of chromosome 20 in pure erythroleukemia.

Chest Wall Swelling, A Rare Presentation of Richter's Transformation.

A large cell lymphoma develops in approximately 1-10% of chronic lymphocytic leukemia (CLL). This is known as Richter's syndrome. Chest wall swelling is a very unusual presentation of this syndrome. Here we report another such case of chest wall swelling, a very rare presentation of Richter's syndrome.