Acute myeloid leukemia with t(4;12)(q12;p13): A morphological dilemma.

Cytogenetics has a pivotal role in risk stratification of acute myeloid leukemia (AML). We report a case of AML with a t(4;12)(q12;p13). To the best of our knowledge, there are about 24 cases of t(4;12) reported in AML which are usually misdiagnosed as lymphoproliferative disorders on morphological assessment. This case showed specific clinical, morphological, and immunophenotypic features such as (1) pseudo lymphoid morphology, (2) dysplasia in granulocytic series, (3) an immature immunophenotype with positivity for CD34 and CD117, and (4) poor treatment response.

Loss of chromosome Y in acute lymphoblastic leukemia: Age related or neoplastic phenomenon.

Loss of chromosome Y (LOY) in the bone marrow has long been considered as an age-related phenomenon with an incidence of more than 25% in males beyond the age of 80 years. Though reported as an acquired abnormality in myeloid neoplasms, it has rarely been described in B-lymphoblastic leukemia which primarily is a disease of the young. We describe here in three cases of pediatric B-lymphoblastic leukemia with LOY. Conventional cytogenetic studies and fluorescence in situ hybridization studies using centromeric probes for chromosome X and Y on peripheral blood samples ruled out constitutional LOY in all the three cases favoring it to be a neoplastic phenomenon.

Mosaic double aneuploidy: Down syndrome and XYY.

Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5‑year‑old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy, Down syndrome and XYY. The karyotype was 47, XY,+21[19]/48, XYY,+21[6]. ish XYY (DXZ1 × 1, DYZ1 × 2). Mosaic double aneuploidies are very rare and features of only one of the aneuploidies may predominate in childhood. Cytogenetic analysis is recommended even if the typical features of a recognized aneuploidy are present so that any associated abnormality may be detected. This will enable early intervention to provide the adequate supportive care and management.

Fluorescence in situ hybridization patterns of BCR/ABL1 fusion in chronic myelogenous leukemia at diagnosis.

Background : Chronic myelogenous leukemia (CML) is characterised by the t(9;22)(q34;q11.2) which results in the formation of the BCR/ABL1 fusion gene. Occasionally, the t(9;22) may be associated with submicroscopic deletions of chromosomes 9 and/or 22 which appear to be associated with a worse prognosis. Three or four-way variant t(9;22) may also occur. All these changes as well as gain of the Philadelphia chromosome which represents disease progression can be detected by fluorescence in situ hybridization (FISH) analysis. FISH analysis at presentation is used to determine the number of cells with BCR/ABL1 fusion and establish whether the patterns are typical or atypical. Response to therapy can then be monitored by serial testing. Patients and Methods : The study group consisted of all patients diagnosed or suspected to have CML who had interphase FISH analysis at presentation on peripheral blood/bone marrow using a commercially available BCR/ABL1 dual colour, dual fusion probe. The study was performed at a tertiary hospital in India between 2004 and 2010. Results: There were 1076 diagnostic samples which were positive for BCR/ABL1 fusion. Typical dual fusion signals (two fusions, one red and one green, 2F1R1G) were seen in 801 cases (74 %). Atypical signal patterns were seen in 275 cases (26%). These were: 1F1R2G (4%), 1F2R1G (2.5%) and 1F1R1G (11%) representing deletions of the derivative 9 involving chromosome 9 sequences, chromosome 22 sequences, or both respectively; 3F1R1G (6.5%) usually representing gain of an additional Philadelphia chromosome and 1F2R2G (1%) representing a three- or four-way variant translocation. More than one signal pattern was seen in 1%. Conclusions: Our findings were similar to the literature with respect to the distribution of signal patterns except that we had a lower number of patients with variant translocations. While each signal pattern is typically associated with a particular abnormality, there can be more than one explanation for each pattern. Hence, metaphase FISH analysis is the "gold standard" for the interpretation of signal patterns.