Cytogenetic and Molecular Features of 1331 Chinese Patients with Primary Acute Lymphoblastic Leukemia (ALL).

Abstract 4718

Cytogenetic-molecular signature plays an important role in diagnosis, treatment and prognosis evaluation in acute lymphoblastic leukemia (ALL). With examination of karyotype and gene rearrangement, we investigated retrospectively the cytogenetic characteristics in 1331 adults and children with primary acute lymphoblastic leukemia (ALL) diagnosed from November 1989 to July 2007.

Cytogenetic and molecular genetic analysis was carried out successfully in 1030 (77.39%) of 1331 cases, abnormal clone was detected in 629 (61.07%) cases. The abnormalities of t(9;22)/BCR-ABL and/or t(4;11)/MLL-AF4 were presented more commonly in adults than in children (25.39% Vs 10.34%,P<0.001; 4.69% Vs 1.68%,P=0.0067). On the contrary, hyperdiploid(>50) was more frequently seen in children than in adults (13.18% Vs 4.30%,P<0.001). In addition, t(8;14)/IGH-MYC,t(12;21)/TEL-AML1 and t(11;19)/MLL-ENL were only observed in pediatric ALL. Compared with data of western countries, t(9;22)/BCR-ABL involvement in Chinese ALL patients, either in adults or in children, was more common. Simultaneously, a lower frequency of t(12;21)/TEL-AML1 was found in Chinese pediatric ALL patients.

Ik6, one of IKZF1 deletion isoforms, was detected in 72.29% of ALL patients with Ph chromosome using reverse transcription-PCR amplification.

In T-ALL, the frequency of the expression of SIL-TAL,CALM-AF10,HOX11,HOX11L2 gene and the mutation of NOTCH1 gene was 12.38%,4.69%,25.49%,24.51% and 32.99%, respectively.

The overall survival of the children was superior to that of the adults, which was the same as previous reports by many other groups. According to the prognosis of patients, these cytogenetic-molecular signatures could be further classified into three subgroups in adult and four subgroups in children. Patients with Ik6 deletion isoform of IKZF1 gene had a significantly worse prognosis than those with wild type isoform (P=0.009). In T-ALL, patients with NOTCH1 mutation were related with poor outcome (P=0.007).