A Sole t(10;19)(p11.2;p12) in AML-ETO negative AML-M2 paediatric patient: First novel case from India

Acute myeloid leukemia (AML) is a heterogeneous group of disorders with regards to its pathology and molecular genetics features. The translocation t(8;21)(q22;q22), which results in the fusion of the AML and ETO genes, is a recurrent aberration in AML, preferentially correlated with FAB- M2, and has the highest incidence in childhood AML. Because of the favorable prognosis, the evidence of the t(8;21) or the AML1-ETO fusion gene is mandatory in most of the therapy trials, allowing the stratification of the patients to the correct risk group in terms of treatment. Here, we describe a novel case of sole translocation t(10;19)(p11.2;p13) in a AML1-ETO negative AML-M2 patient. In general, this translocation is previously observed with combination of complex translocations, but sole abnormality was not previously observed. This is a novel translocation and not observed previously as a sole abnormality in any AML case. Hence, the functional role of this translocation is still unknown. Short term bone marrow culture was carried out for conventional cytogenetics and karyotype was 46, XX,t(10;19)(p11.2;p12) in all 20 metaphases analyzed. To confirm this translocation FISH with Whole chromosome paint probe was applied and results confirmed the translocation between chromosome 10 and 19. To the best of our knowledge, this is the first novel case of sole t(10;19) in a paediatric AML-M2 patient with AML-ETO negative fusion. Patient expired within a week. Therefore, the present case challenges the view that the occurrences of sole and new novel translocation require more such cases to be studied in large cohort which is generally an indication for poor prognosis.

Trisomy 8 in leukemia: A GCRI experience.

Trisomy of chromosome 8 is frequently reported in myeloid lineage disorders and also detected in lymphoid neoplasms as well as solid tumors suggesting its role in neoplastic progression in general. It is likely to be a disease-modulating secondary event with underlying cryptic aberrations as it has been frequently reported in addition to known abnormalities contributing to clinical heterogeneity and modifying prognosis. Here, we share our findings of trisomy 8 in leukemia patients referred for diagnostic and prognostic cytogenetic assessment. Total 60 cases of trisomy 8, as a sole anomaly or in addition to other chromosomal aberrations, were reported (January 2005–September 2008). Unstimulated bone marrow or blood samples were cultured, followed by GTG banding and karyotyping as per the ISCN 2005. Patients with +8 were chronic myeloid leukemia (CML) (36), acute myeloid leukemia (AML) (17), and acute lymphoblastic leukemia (ALL) (7). In 7 patients, trisomy 8 was the sole anomaly, whereas in 6 patients +8 was in addition to normal clone, in 47 patients, the +8 was in addition to t(9;22), t(15;17), and others, including 3 with tetrasomy 8. Only one patient showed constitutional +8. The present study will form the basis of further cumulative studies to correlate potential differential effects of various karyotypic anomalies on disease progression and survival following a therapeutic regime. To unravel the role of extra 8 chromosome, constitutional chromosomal analysis and uniparental disomy will be considered.

AML-M2 with der(18)t(1;18)(q2?;p11.3) in addition to t(8;21) and del(9q).

We report a case of Acute Myeloid Leukemia with clinical features suggestive of AML-M3 and 46,XX,t(8;21),del(9q),der(18)t(1;18) karyotype leading to the final diagnosis AML-M2 in light of t(8;21). The Deletion (9q) is a frequent secondary anomaly to the t(8;21)(q22;q22) in AML-M2. In addition to these two AML-M2 related rearrangements we also observed der(18)t(1;18)(q2?;p11.3) which may be an unusual rearrangement. This rearrangement resulted into partial trisomy of chromosome #1(q2?) without the loss of any part of chromosome 18, morphologically. Rearrangements of long arm of chromosome 1 that result in complete or partial trisomy for 1q mostly involved the region q25-q32, which may confer a proliferation advantage.

Loss of sex chromosome in acute myeloid leukemia.

Loss of sex chromosomes has been reported in normal and malignant marrows and its frequency increases with age in both situations. It is not clear whether the sex chromosome loss is a critical mutational event for neoplastic transformation or a genetic change related to ageing. The present study was undertaken to analyze incidence of loss of sex chromosomes in leukemia patients. Karyotypic analysis in bone marrow cells was carried out in total 270 AML patients registered at G.C.& R.I. during January 2000 to October 2003. Out of 270, 22 patients had loss of sex chromosome in addition to other disease specific chromosomal abnormalities. Out of 22 patients, 50% (11 of 22) were of the pediatric age (up to 14 years), and only 10% (3 of 22) patients were above the age of 50 years, maximum age being 65 years. On follow-up, only in patients with pathological remission normal 46XX/XY karyotypes were seen. Whereas in patients with persistent leukemic activity, clones with loss of sex chromosome were observed. The results indicate that sex chromosome loss in these cases may be equivalent of a clonal cytogenetic process rather than related to ageing process.