EVIDENCE FOR SPECIFIC IMMUNE-RESPONSE AGAINST P210 BCR-ABL IN LONG-TERM REMISSION CML PATIENTS TREATED WITH INTERFERON

Interferon-alpha treatment induces complete cytogenetic remission in 2 5% of Philadelphia chromosome (Ph)-positive chronic myelogenous leukem ia (CML) patients. These remissions are durable unlike remissions indu ced with other therapies and yet residual leukemia is detectable in mo st of these patients. Total peripheral blood mononuclear cells (PBMCs) from CML patients in long-term remission following interferon treatme nt exhibited significantly higher proliferative responses (four- to 15 -fold over background) than normals directed against P210 BCR-ABL in e xtracts of transfected monkey fibroblast cells. Surprisingly, similar enhanced levels of specific proliferative responses were observed with extracts from cells expressing Bcr and/or Abl proteins. in contrast, extracts from vector only or v-Mos-expressing cells had background lev el responses. Control monkey fibroblast cells lacking BCR-ABL expressi on failed to induce proliferation over background levels. Normal indiv iduals had no significant responses to Bcr/Abl extracts. On the other hand, peripheral blood mononuclear cells from allogeneic bone marrow t ransplant CML patients had proliferative responses to cell extracts in dependent of Bcr-Abl. These data indicate that patients in remission d ue to alpha-interferon treatment have significantly higher levels of s pecific cellular immunoreactivity against Bcr/Abl sequences than norma l controls, which could play a role in maintaining cytogenetic remissi on in Ph-positive CML patients.