FLT3 and NPM-1 mutations in a cohort of acute promyelocytic leukemia patients from India.

Background: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) and is reported to show better response to anthracyclin based chemotherapy. A favorable overall prognosis over other subtypes of AML has been reported for APL patients but still about 15% patients relapse. Methods: This study evaluated the presence of Famus like tyrosine kinase‑3 (FLT3) and nucleophosmin‑1 (NPM1) gene mutations in a cohort of 40 APL patients. Bone marrow/peripheral blood samples from patients at the time of diagnosis and follow‑up were processed for immunophenotyping, cytogenetic markers and isolation of DNA and RNA. Samples were screened for the presence of mutations in FLT3 and NPM1 genes using polymerase chain reaction followed by sequencing. Results: Frequency of FLT3/internal tandem duplication and FLT3/tyrosine kinase domain was found to be 25% and 7% respectively. We observed a high frequency of NPM1 mutation (45%) in the present population of APL patients.

CD34 positive-microgranular variant of acute promyelocytic leukemia in a child.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) in which abnormal promyelocytes predominate. APL is rare in children (approximately 10% of childhood AML) and is characterized by a higher incidence of hyperleukocytosis, an increased incidence of microgranular morphology, the presence of balanced t(15;17)(q22;q11.2-12) translocation, and more frequent occurrence of the PML-RARα isoforms bcr 2 and bcr 3 compared to adults. The cytomorphology of microgranular variant blasts is obviously different from AML M3 blasts; these cells have a nongranular or hypogranular cytoplasm or contain fine dust-like cytoplasmic azurophil granules that may not be apparent by light microscopy. This case report emphasizes the importance of a high index of suspicion for the diagnosis of APL, the hypogranular variant in particular. They are responsive to differentiation therapy with all trans-retinoic acid and complete remission in seen in >80% cases.

Molecular basis for the diagnosis and treatment of acute promyelocytic leukemia

Acute promyelocytic leukemia is characterized by gene rearrangements that always involve the retinoic acid receptor alpha on chromosome 15. In the majority of patients t(15;17) is detected, which generates the promyelocytic leukemia gene/retinoic acid receptor alpha rearrangement. This rearrangement interacts with several proteins, including the native promyelocytic leukemia gene, thus causing its delocalization from the nuclear bodies, impairing its function. The immunofluorescence staining technique using the anti-PML antibody may be used to provide a rapid diagnosis and to immediately start therapy using all-trans retinoic acid. The experience of the International Consortium on Acute Promyelocytic Leukemia has demonstrated that early mortality was significantly reduced by adopting the immunofluorescence technique. All-trans retinoic acid combined with chemotherapy is the standard therapy; this promotes complete remission rates greater than 90% and cure rates of nearly 80%. However, early mortality is still an important limitation and hematologists must be aware of the importance of treating newly diagnosed acute promyelocytic leukemia as a medical emergency.

Specific chromosomal abnormalities in patients with acute nonlymphocytic leukemia from the Islamic Republic of Iran.

Cytogenetic analysis performed at diagnosis is considered to be the most valuable prognostic factor in acute non-lymphocytic leukemia (ANLL), a very heterogeneous disease. Little data exist in Iran regarding the cytogenetic characteristics of ANLL . Therefore, cytogenetic investigations were performed for 58 patients with various subtypes of ANLL with unstimulated short term culture and high resolution cell synchronization techniques. Among the 58 evaluated patients, 45 (77.5%) showed clonal karyotypic abnormalities and the percentages of the abnormal cells were recorded within the range of 30%-100%. Some 14 were classified as M1, 20 as M2, 19 as M3 , 3 as M4, 1 as M5 and 1 as M6. The most common chromosome rearrangements were t(15;17), t( 8;21) and t(9;22). Trisomy of chromosome 8 (+8) was the most frequent numerical alteration in 3 patients with M1, M2 and M6. The incidence of other chromosomal defects, including -10, DMCs , -19 , 5q- , dicentric(dic), chromatid breaks, and marker chromosomes was relatively high. Similarities and dissimilarities of our study with others may be due to the role of genetic sensitivities as well as uneven geographic distribution in the pathogenesis of ANLL. Further prospective studies are warranted to precisely elucidate ethnic differences in the pathogenesis of this disease in different populations.