[Characteristics of malignant clone from acute lymphocytic leukemia]

To identify the characteristics of malignant clones in leukemia.

VH region of B lymphocytes from children with ALL, patients with MM, and tissues from fetuses obtained by induced labor at different gestational stages was amplified using RT-PCR method with one primer located in VH1, VH2, VH3, VH4, VH5, or VH6 and another primer at the join region. The PCR products were then separated on sequencing gel and their VH gene fingerprints were obtained. The fingerprints from tissues of fetal liver, spleen, thymus and bone marrow, and bone marrow B cell from 15 cases of ALL and one case of MM were compared, and VH repertoire information were deduced from those fingerprints.

The VH6 family was the dominant family in fetal liver and the VH3 family occurred predominantly in fetal spleen and bone marrow. Monoclonal proliferation of B lymphocytes was found in 9 of the 15 patients with ALL. Of these 9 cases, proliferation of VH1 was found in 3 cases, proliferation of VH6 was found in 3 cases, and proliferation of both VH3 and VH4 in 2 cases. The VH families other than leukemic clone(s) in these patients were in normal distribution or suppression status. Oligoclonality was found in one ALL case with malignant growth of VH1, VH3 and VH6. Polyclonality with nearly normal spectrum of VH1-VH6 was detected in 6 of the 15 cases. DNA sequencing of a VH3 clone from an ALL case demonstrated a similarity to the sequence of embryonic clone from a fetus of gestational age of 13 weeks. The VH sequence of one adult MM case, with hypermutation of somatic cell, was remarkably different from that of the germline.

Rearrangement of VH1, VH3, VH4 and VH6 can be frequently found in ALL. It is unlikely that leukemia in childhood originates from stimulation of foreign antigens.