Importance of FISH combined with Morphology, Immunophenotype and Cytogenetic Analysis of Childhood/Adult Acute Lymphoblastic Leukemia in Omani Patients

Abstract

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.

Cytogenetics Findings of Patients With Acute Lymphoblastic Leukemia in West Indian Region.

“…This result is comparable to the findings in the earlier studies (Safaei et al, 2013). The incidence of normal karyotype in the previous studies is reported as 48.32% (Siddaiahgari et al, 2015) and 38.30% (Safaei et al, 2013) while it was 31.42% in our study maybe, due to the improvement in the culture techniques and introduction of interphase FISH technique, which led to higher detection of chromosomal abnormalities as in many other studies which used FISH (Goud et al, 2015).…”

“…The detection can be done by conventional cytogenetic method like karyotyping and molecular cytogenetic techniques like Fluorescent in-situ hybridization (FISH). These methods are helpful in assessing the classification, risk stratification and prediction of outcome of ALL patients (Goud et al, 2015).…”

“…In this study interphase-FISH was used as a complementary method along with G-banding for some ALL patients to confirm cytogenetic findings and for the poor quality samples or slides with no metaphases. The combination of both the method can improve the detection of genetic abnormalities (Goud et al, 2015).…”

“…Many studies have been conducted on ALL, based on the cytogenetic findings of the patients with ALL (Safaei et al, 2013;Siddaiahgari et al, 2015), FISH analysis of childhood and adult ALL patients (Goud et al, 2015) and Epidemiology of childhood cancers in India (Arora et al, 2009). Also, studies based on significant fusion oncogenes in patients with ALL have been conducted (Sabir et al, 2012).…”

del(5q) in acute lymphoblastic leukemia (ALL)

“…Excluded are patients with EBF1/PDGFRB fusion that arose from interstitial deletion of 5q33, occurring within the Philadelphia-like ALL subtype. Del(5q) as a sole clonal cytogenetic abnormality was found in 11 patients (3 with B-ALL, 4 with T-ALL and 4 with unspecified ALL) (Kowalczyk et al, 1985;Brusamolino et al, 1988;Raimondi et al, 1988;Loncarevic et al, 1999;Midmer et al, 1999;Gmidene et al, 2008;Palau et al, 1991;Valtat et al, 1991;Theodossiou et al, 1992;Goud et al, 2015).…”