CHROMATIN NUCLEOPROTEIN COMPLEXES CONTAINING TIGHTLY BOUND C-ABL, P53AND BCL-2 GENE-SEQUENCES - CORRELATION WITH PROGRESSION OF CHRONIC MYELOGENOUS LEUKEMIA

We previously developed a technique to isolate subchromatin nucleoprot ein complexes (NPC) that contain tightly bound genes and enzymatic act ivities. NPC fractions (NPCF) were prepared by directly treating isola ted nuclei with MspI to generate six NPCF (S1, M1, S2, M2, 0.1K and R) . The NPCF have been used to predict the potential efficacy of interfe ron-alpha (IFN-alpha) treatment in patients with chronic myelogenous l eukemia (CML) [Nicolson et al., Gene 159 (1995) 105-111]. Here, the NP CF were probed for the presence of tightly bound c-abl, p53 and bcl-2 genes. We found that the NPCF isolated from the nuclei of leukocytes o f normal individuals rarely contained detectable quantities of tightly -bound c-abl, p53 or bcl-2 genes or gene sequences, whereas in CML nuc lei these genes were often found in tight association with multiple NP CF. Examination of TPCF isolated from the leukocyte nuclei from patien ts with highly progressive CML for the presence of the three genes rev ealed that more NPCF contained the three tightly-bound genes than leuk ocyte NPCF from patients with stable or less progressed CML. These dat a suggest that as CML progresses to more malignant states, oncogenes, suppressor genes and apoptosis-associated genes become tightly associa ted with NPCF.