Interferon-α directly inhibits DNA polymerase activity in isolated chromatin nucleoprotein complexes: correlation with IFN-α treatment outcome in patients with chronic myelogenous leukemia

Nucleoprotein gene tracking: Localization of specific HIV-1 genes to subchromatin nucleoprotein complexes containing endonuclease activity in HIV-1-infected human cells

“…In these studies, we were able to demonstrate that CML patients whose leukocyte nuclear NPC fractions contained DNA polymerase activity sensitive to in vitro inhibition by IFN-␣ were entirely from patients that were responsive to the in vivo administration of this cytokine. By contrast, patients whose leukocyte NPC fractions were insensitive to in vitro inhibition by IFN-␣ were unresponsive to the in vivo administration of IFN-␣ (Nicolson et al, 1995]. Thus, we were able for the first time to predict cytokine responsiveness in the clinical setting.…”

“…We also found that that multiple NPC fractions from the leukocytes of CML patients with more progressive disease contained more c-abl, p53, and bcl-2 gene sequences than the same NPC fractions from CML patients with less advanced disease [Nicolson et al, 1996]. Since the NPC fractions from CML patients contained transcription-and proliferation-associated enzymes [Rosenberg-Nicolson and Nicolson, 1992a,b;Nicolson et al, 1995], the results suggested a possible role for certain tightly bound genes in the progression of CML. Further research will be necessary to confirm or not the notion that particular NPC may be involved in the progression of CML.…”

“…NPGT has been used to analyze NPC fractions from various cell systems for the presence of specific genes as well as enzymatic activity. For example, we have screened NPC from metastatic variants of the murine large cell lymphoma for the presence of abl, p53, c-neu, c-H-ras, ␤-casein, 18S rDNA, and µ-chain immunoglobulin genes and found that these genes were differentially expressed in the highly metastatic variants [Rosenberg-Nicolson and Nicolson 1992b;Nicolson and Nicolson, 1992b, 1993,1994aNicolson et al, 1995;1996]. We also used RNA back-hybridization assays to determine whether individual nuclei-derived NPC are capable of synthesizing mRNA in vitro that could back-hybridize to specific genes, indicating the presence of enzymatic activities capable of producing RNA with specific sequences capable of hybridizing back to the gene sequences from which they were derived.…”

FISH analysis for CML monitoring ?

“…After chemotherapy and IFN treatment the leukemic bulk is greatly reduced, so that the relatively higher rate of normal cells detected by interphase FISH might be due mainly to the gross reduction of BCR-ABLc cells. Probably IFN treatment, as suggested by the cytogenetic data, is slow in reducing the proliferative rate of the Phc clone, and the diminished percentage of BCR-ABLc cells detected by dc-FISH is a result of micro-environmental changes or of a restored apoptotic mechanism, induced by IFN [23][24][25][26], that causes more Phc cells to die. On clinical grounds the finding that all of our patients had a decreased percentage of BCR-ABLc cells after therapy might suggest that all CML patients are potentially responsive to IFN.…”