28 - Insertion of miRNA125b-1 into immunoglobulin heavy chain gene locus mediated by V(D)J recombination in precursor B cell acute lymphoblastic leukemia

Summary

Introduction

Acute lymphoblastic leukemia (ALL) is a malignant tumor of progenitor cell committed to an immunophenotypically and genetically differential pathway of lymphoid lineage. The leukemic cells lose the property of further differentiation and gain the ability of autonomic proliferation, allowing clonal expansion of the malignant cells in the bone marrow. The bone marrow, which is replaced by enormous leukemic cells, no longer produces sufficient normal blood cells, so that individuals suffering from this disease show a reduced number of red blood cells, platelets and normal white blood cells. In addition to expansion in the bone marrow, the leukemic cell can infiltrate other organs such as lymph nodes, spleen, liver, central nervous system, and gonads; and sometimes develops solid tumor called lymphoblastic lymphoma (Head, 2004; Berg et al., 2005; Pui, 2006).

The lymphoid cells express cell surface antigens sequentially during the differential pathway (Figure 28.1). Since ALL cells share many of the features of normal lymphoid progenitor cells, the vast majority of ALL cells can be broadly classified by their cellular origins using cytochemical and immunophenotypic analyses into precursor B-cell ALL, B-cell ALL and precursor T-cell ALL (Figure 28.1). The most common ALL is the precursor B-ALL, the second T-ALL, and the third B-ALL, which account for ∼75%, ∼20%, and ∼5% of all ALL patients, respectively. The precursor B-cell ALL is defined by cell surface expression of B-lineage associated antigens including CD19, HLA-DR and CD10.