1990 | Y. Yufu, J. Nishimura, H. Ideguchi & H. Nawata
This study investigates the synthesis of heat shock proteins (hsp) in normal human lymphocytes and leukaemic cells to explore potential differences that could explain the selective killing of leukaemic cells by heat. The researchers isolated mononuclear cells from normal volunteers and patients with various types of leukaemia and lymphoma, including acute myelogenous leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myelogenous leukaemia in blastic crisis (CML-bc), adult T cell leukaemia (ATL), chronic lymphocytic leukaemia (CLL), and non-Hodgkin's malignant lymphoma (ML). They used 35S-methionine labeling and electrophoretic techniques to analyze hsp synthesis under heat shock conditions.
The results showed that normal lymphocytes exhibited a typical response to heat shock, with the induction of major hsp (hsp90, hsc70, and hsp70). In contrast, leukaemic cells displayed heterogeneous responses, categorized into three distinct patterns: (a) all three major hsp were inducible, similar to normal lymphocytes; (b) hsp90 and hsp70 were inducible, but hsc70 was not; (c) hsp90 and hsp70 were inducible, with a significant amount of constitutive hsc90 detected. The study also found that immature leukaemic cells frequently lacked hsc70 induction, while more mature cells showed varying degrees of hsc70 inducibility.
Additionally, the researchers examined hsp synthesis in differentiating HL-60 cells, which showed enhanced inducibility of hsc70 along with increased synthesis of hsp90 and hsp70. These findings suggest that the selective induction of hsp in leukaemic cells may play a role in their vulnerability to heat-induced damage, potentially making hyperthermia a viable treatment modality for leukaemia.This study investigates the synthesis of heat shock proteins (hsp) in normal human lymphocytes and leukaemic cells to explore potential differences that could explain the selective killing of leukaemic cells by heat. The researchers isolated mononuclear cells from normal volunteers and patients with various types of leukaemia and lymphoma, including acute myelogenous leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myelogenous leukaemia in blastic crisis (CML-bc), adult T cell leukaemia (ATL), chronic lymphocytic leukaemia (CLL), and non-Hodgkin's malignant lymphoma (ML). They used 35S-methionine labeling and electrophoretic techniques to analyze hsp synthesis under heat shock conditions.
The results showed that normal lymphocytes exhibited a typical response to heat shock, with the induction of major hsp (hsp90, hsc70, and hsp70). In contrast, leukaemic cells displayed heterogeneous responses, categorized into three distinct patterns: (a) all three major hsp were inducible, similar to normal lymphocytes; (b) hsp90 and hsp70 were inducible, but hsc70 was not; (c) hsp90 and hsp70 were inducible, with a significant amount of constitutive hsc90 detected. The study also found that immature leukaemic cells frequently lacked hsc70 induction, while more mature cells showed varying degrees of hsc70 inducibility.
Additionally, the researchers examined hsp synthesis in differentiating HL-60 cells, which showed enhanced inducibility of hsc70 along with increased synthesis of hsp90 and hsp70. These findings suggest that the selective induction of hsp in leukaemic cells may play a role in their vulnerability to heat-induced damage, potentially making hyperthermia a viable treatment modality for leukaemia.