Leukemia, Lymphoma & Myeloma

00:01 Let us look at tumors of the immune system.

00:04 Leukemia develops in the bone marrow.

00:07 There are a number of different types of leukemia.

00:11 The main ones are acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia and chronic myeloid leukemia.

00:23 There are subtypes of each of these types of leukemia.

00:28 Lymphomas in contrast develop in the lymphatic system.

00:33 Two main lymphomas are Hodgkin lymphoma and Non-Hodgkin lymphoma.

00:41 Myelomas are tumors of plasma cells.

00:46 Here we have a stem cell that is giving rise to pre-B lymphocytes.

00:54 Acute lymphoblastic leukemia is usually derived from immature pre-B cells.

01:02 Blasts are present in the bone marrow and blood.

01:05 In chronic lymphocytic leukemia and lymphoma, the malignant population is mature B-cells.

01:14 In CLL, malignant cells are present in the blood.

01:18 In lymphoma, the malignant cells are present in the lymph node and sometimes in other tissues.

01:24 Plasma cells give rise to myeloma.

01:28 In myeloma, the clone of malignant plasma cells produces a monoclonal immunoglobulin; in other words, all the antibody is absolutely identical because it’s derived from a malignant clone of plasma cell.

01:45 T-cell malignancies are somewhat less common.

01:49 T-cells are not infected by Epstein-Barr virus, which is a major way in which B-cells can become malignant.

01:56 Also T-cells are somewhat more susceptible to apoptosis, and therefore less able to survive.

02:06 There are also myeloid leukemias derived from myeloid progenitors as well as these lymphoid leukemias that you can see on this slide.

02:17 Chronic lymphocytic leukemia is rather unusual, in that the leukemic cells have on their cell surface, a molecule that is normally present on B-cells, but also a molecule that is normally present on T-cells.

02:31 As you can see in this flow cytometry diagram, there are normally CD19+ B-cells, and then separately CD5+ T-cells.

02:45 However, in chronic lymphocytic leukemia, the cells express both of those molecules on their surface.

02:51 In other words, a molecule that is characteristic of B-cells, but also a molecule that is more normally characteristic of T-cells.

02:58 Post-transplant lymphoma can arise due to EBV infection in individuals that are receiving immunosuppression in order that they do not reject a transplanted tissue or organ.

03:14 Prior to a renal transplant, this woman had memory T-cells responding to Epstein-Barr virus.

03:21 The Epstein-Barr virus infection was controlled by the T-cells.

03:26 However following a transplant, the immunosuppressive drug cyclosporine has made the memory cells non-responsive.

03:35 And there is a polyclonal increase in EBV infected B-cells.

03:42 There becomes a situation in which there is uncontrolled EBV infection which drives B-cell proliferation.

03:55 The polyclonal B-cell proliferation will improve if the cyclosporine is stopped.

04:01 However with ongoing proliferation, Myc translocation can occur within the B-cells.

04:11 There is a malignant transformation resulting from this Myc translocation, and the development of lymphoma.

04:20 The polyclonal growth of B-cells has increased the risk for this translocation to occur.

04:26 The monoclonal B-cell proliferation will continue after cyclosporine is stopped, and the patient develops the symptoms of lymphoma.

04:38 In multiple myeloma, there are plasma cells in the bone marrow that become malignant.

04:47 And therefore, a clone of rapidly replicating plasma cells pumping out huge amounts of antibody of a single specificity develop.

05:00 They produce what is referred to as a paraprotein.

05:04 And this can be detected on a electrophoretic gel.

05:07 We can see the paraprotein band in the gamma region from the patient on this gel.

05:15 In contrast, in a healthy individual, that monoclonal band is missing because their antibodies are totally polyclonal; a very huge mixture of different specificities.