Blood Cancer Flashcards
(20 cards)
Describe the altered cell fate in myelodysplasia
Increased apoptosis Reduced number terminally differentiated cells produced Partial block in differentiation leDs to the accumulation of immature cells
List some therapeutic targets for acute myeloid leukaemia
Mutations in proliferation and survival FLT3 Oncogenic RAS KIT alleles PTPN11 - FLT3 inhibitors Mutations in differentiation and self-renewal Core binding factor Retinoic acid receptor MLL rearrangement -ATRA Target self-renewal WNT, notch, BMI1, HOX
Describe the epigenetic of acute myeloid leukaemia
In the cancer cell DNMT, HDAC and MBP methylate
List some single gene molecular abnormalities in acute myeloid leukaemia
FLT3 c-KIT CEBPalpha RUNX1 RAS NPM1 MLL partial tandem duplication WT1 IDH1/2 TET2 DNMT3A BCOR
List the important transcription factors in blood cell differentiation
RUNX1 GATA2 C/EBPalpha DNMT3A TET2
Give an example of a fusion protein in cancer and its treatment
PML-RARA Produced by the t(15:17) translocation in leukaemia Prevents transcription and therefore prevents cell differentiation Treat with retinoic acid which binds to the Retinoic Acid Receptor and releases the conplex that prevents transcription
Describe core binding factor translocations in acute leukaemia
AML1-ETO aka RUNX1/RUNX1T1 Blocks differentiation at myeloblast stage
Briefly describe FLT3 in acute myeloid leukaemia
Receptor tyrosine kinase ➡️RAS ➡️Akt Mutation leads to permanent activation, and continuous proliferation Associated with lower survival
Summarise myeloproliferative disease
Excess of myeloid cells Primary polycythaemia- too many RBCs Primary thrombocythaemia- too many platelets Idiopathic myelofibrosis- too much marrow fibrosis Chronic myeloid leukaemia (CML)- too many neutrophils
Summarise chronic myeloid leukaemia
Accumulation of myeloid progenitors High white blood cell count Large spleen Can transform into acute leukaemia
What is the significance of Imatinib
BCR-Abl is a fusion protein that forms a tyrosine kinase with a markedly increased activity Imatinib inhibits the binding of ATP to ABL tyrosine kinase Selective for cancer cells
List some next gen BCR ABL inhibitors and why are they needed
Nilotinib Dasatinib Bosutinib Ponatinib Needed to overcome the cancer cell mutations to overcome Imatinib, eg. Ponatinib is the only one that will work against the T315I mutation
Summarise classical myeloid proliferative neoplasm
Polycythaemia Vera- increased red cell precursors in bone marrow Essential thrombocythaemia- increased megakaryocytes in marrow Large spleen Thrombosis Haemorrhage Itching Gout Clonal mutations- JAK2, CALR, MPL Treatment- aspirin, venesection, cytoreductive agents
Summarise myelofibrosis
Fibrotic marrow Cytopenias Very large spleen -asymptomatic -spleen pain -fevers, sweats, back pain -infections Often a poor prognosis Blood transfusions Treatment- thalidomide, medroxyprogesterone, Ruxolitinib-JAK inhibitor
Summarise myeloproliferative disease
Excess of myeloid cells Primary polycythaemia- too many RBCs Primary thrombocythaemia- too many platelets Idiopathic myelofibrosis- too much marrow fibrosis Chronic myeloid leukaemia (CML)- too many neutrophils
List some lymphoid classifications
Precursor B/T neoplasms- acute lymphoblastic leukaemia (ALL) Mature B cell neoplasms- B cell lymphoma Mature T and NK cell neoplasm- T cell lymphoma Hodgkin lymphoma Immune deficiency associated lymphoproliferative disease
Summarise chronic lymphocytic leukaemia
Proliferation of mature B cells Can infiltrate lymph nodes and spleen Indolent lymphoproliferative disease Mostly elderly
Summarise multiple myeloma
Monoclonal proliferation of plasma cells Lytic bone lesions- fractures Paraprotein- renal failure Marrow suppression- anaemia
What is the significance of EBV in lymphoma?
EBV infection leads to a latent pool of infected B lymphocytes which if coupled with immune suppression➡️ continued growth in a sense of immune control➡️ post transplant lymphoproliferative disease With chronic malaria➡️ chromosomal translocation and CMYC activation➡️ Burkitt lymphoma With co-factors➡️ cellular genetic changes➡️ Hodgkin lymphoma EBV encoded nuclear antigens (EBNA) can repress gene expression
Name some underlying similar pathogenesis abnormalities found in lymphoproliferative diseases
Cytogenetic abnormalities- hyper diploid, the Philadelphia chromosome (BCR-ABL) Translocations forming fusion proteins- t(8;14) CMYC-IGH in burkitts Abnormalities in bone marrow microenvironment Some bacteria and viruses with other factors like immune suppression can cause some important lymphomas
