Establishment of a novel human lymphoblastic cell strain with the long arm of chromosome 11 aberration without MLL rearrangement

Abstract

At present, all cell strains derived from acute lymphoblastic leukemia (ALL) patients with the long arm of chromosome 11 aberration are accompanied with mixed lineage leukemia (MLL) gene rearrangement. In this study, we established a permanent ALL cell strain CHH-1 with the long arm of chromosome 11 aberration and without MLL rearrangement, hoping that it could be used for the research of ALL with such genetic abnormality. CHH-1 cell strain was certified through morphology, immunophenotype, genetics and immunoglobulin (Ig) gene rearrangement analysis. Cell characteristics including tumorigenic ability, semisolid colony forming ability, telomerase activity, autocrine and invasion were further detected. Cells were with an add(11)(q23) structural abnormality without MLL rearrangement, and were consistent with the genetic abnormality of the patient. In addition, these cells had features of tumor-forming ability, high colony forming capacity, unique cytokine autocrine mode, high telomerase activity, and high invasion ability. CHH-1 may prove to be a useful cell model for the research of human leukemia with genetic aberration in chromosome 11, and help explore the role of such genetic abnormality in the pathogenesis, progression and prognosis of ALL, and in developing new target drugs.Acute lymphoblastic leukemia (ALL) is a malignancy that originates from hematopoietic precursors of the lymphoid lineage. A purely leukemic presentation is most typical of B lineage ALL (85%) 1 . It is the most common leukemia in children, which accounts for approximately 80% of all leukemias in this group and 20% in adults. The complete remission (CR) rate of adult ALL ranges from 70% to 90%, with a 5-year overall survival (OS) rate of below 30% due to its high relapse rate 2 . With the advances in cytogenetic and molecular techniques over the past 20 years, our understanding about the biology and pathogenesis of leukemia has progressed tremendously. Chromosomal abnormalities have become increasingly significant biomarkers in the diagnosis, prognostics, detection of residual disease and targeted therapy of ALL. The normal number of chromosomes with structural abnormalities is the most frequent abnormal karyotype in adult ALL 3,4 . Structural abnormalities in the long arm of chromosome 11 are frequently found in ALL, and are associated with poor prognosis 5 . Recently, most studies have focused on MLL gene rearrangement at 11q23 6 . However, the MLL gene is not rearranged in most of other cases, suggesting that these patients may have breakpoints at 11q22-q25 beyond the MLL gene. A previous study 7 analyzed 40 adult leukemia