Molecular Cytogenetic Analysis of Gene Rearrangements in Childhood Acute Lymphoblastic Leukemia

Abstract

The aims of this study were to estimate the incidences of BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions in childhood acute lymphoblastic leukemia (ALL), to identify new abnormalities, and to demonstrate the usefulness of interphase fluorescence in situ hybridization (FISH). We performed G-banding analysis and FISH using probes for BCR/ABL, MLL, TEL/AML1 rearrangements, and p16 deletions on 65 childhood ALL patients diagnosed and uniformly treated at a single hospital. Gene rearrangements were identified in 73.8% of the patients using the combination of G-banding and FISH, while the chromosomal abnormalities were identified in 49.2% using G-banding alone. Gene rearrangements were disclosed by FISH in 24 (72.7%) of 33 patients with normal karyotype or no mitotic cell in G-banding. Among the gene rearrangements detected by FISH, the most common gene rearrangement was p16 deletion (20.3%) and the incidences of others were 14.1% for TEL/AML1, 11.3% for MLL, and 1.8% for BCR/ABL translocations. Infrequent or new aberrations such as AML1 amplification, MLL deletion, ABL deletion, and TEL/AML1 fusion with AML1 deletion were also observed. We established the rough incidences of gene rearrangements in childhood ALL, found new abnormalities and demonstrated the diagnostic capability of interphase FISH to identify cryptic chromosome aberrations.

FISH Analysis of 9p21 Deletion in Egyptian Childhood Acute Lymphoblastic Leukemia Patients: Relation to Prognosis and Disease Outcome

“…As regards prognostic risk stratification, the present study showed that 66.7% in high risk category had 9p21 deletion. This come in line with Woo et al [18] and Karkucak et al [19] who reported that 64.3% and 66% of their patients respectively in high risk group had 9p21 deletion. Karkucak et al [19] concluded that 9p21 deletion was the most common abnormality among high-risk patients.…”

“…This comes in line with four large studies by Woo et al [18] , Mullighan et al [21] , Perez-Vera et al [22] and Sulong et al [10] , they utilized FISH technique with a commonly used commercial probe to study 9p21 deletion in patients with ALL and the deletion frequency ranged from 20-27%. On the other hand this frequency is higher than that recorded by Kuchinskaya et al [12] who identified this deletion in (15.7%) of patients, but is lower than a study done by Schiffman et al [4] who reported this deletion in 29/45 (64.4%) patients and Karkucak et al [19] who detected 9p21 deletion in 8/22 (36%)of patients.…”

“…Moreover, the presence of 9p21 deletion was found to be related to tumor burden as it was significantly associated with hepatomegaly and splenomegaly. Considering laboratory data, 5/12 (41.7%) of 9p21 deletion positive patients presented with WBCs ≥50 x10 9 /L, Woo et al [18] and Kuchinskaya et al [12] reported initial WBCs count >50 x10 9 /L in (50%) and (23.6%) in their studied patients respectively. As regards prognostic risk stratification, the present study showed that 66.7% in high risk category had 9p21 deletion.…”

“…Similarly Karkucak et al, [19] reported age range of 3-14years with 50% <10 years and 50% > 10 years. On the other hand, Woo et al [18] reported that 28.6% of 9p21 deletion positive patients have age <1+>10 years and 71.4% of them have age (1-10) years.…”

“…It is well established that the identification of cytogenetic abnormalities is very useful for the prediction of outcome in childhood ALL [18] . Although some of these abnormalities are accepted as favorable or poor prognostic factors, the prognostic effects of others have not been well determined [19] .…”