introduction to haematological malignancies Flashcards
what is the life span of RBC ?
120 days
what is the life span of platelets ?
10 days
what are the hematopoetic stem cells ?
lymphoid stem cells
pluripotent stem cells
myeloid stem cells
what to lymphoid stem cells give rise to ?
plasma cells/ B cells
T cells
what do pluripotent stem cells give rise to ?
lymphoid and myeloid stem cells
what do myeloid stem cells give rise to ?
RBCs Platelets neutrophils monocytes eosinophils
what is the origin of haematological malignancies ?
they are of single cell origin
what are the features of acute leukemia ?
cells are blocked at an early stage of differentiation
rapidly growing
associated with early bone marrow failure
what are the symptoms of bone marrow failure ?
anemia
thrombocytopenia
neutropenia
what are the symptoms of tissue infiltration?
lymphadenopathy
gum hypertrophy
rash, subcutaneous chloromas
CNS infiltration
what is the clinical presentation of acute leukemia ?
splenomegaly
retinal haemorrhages
blast cells in blood film
gum hypertrophy
what is the treatment for acute leukemias?
stabilize the patient , treat any infections, stop bleeding, transfuse
start induction chemotherapy ( induction)
several courses of chemotherapy (maintenance)
how is prognosis decided in acute leukemia ?
based on response to induction chemotherapy and the presence of genetic alterations which activate particular oncogenes
what are the features of chronic leukemias ?
fully differentiated cells predominate
with accumulation of these mature cells
slower in growth
bone marrow failure is usually later in the disease
untreated chronic myeloid leukemia cases ?
progression to acute leukemia overtime
What is the common translocation in chronic myeloid leukemia (CML)?
9;22 Bcr:Abl fusion , Philadelphia chromosome
what does the hybrid protein created by Bcr;Abl fusion promote ?
increased proliferation , decreased apoptosis ( increased tyrosine kinase activity)
what is chronic lymphocytic leukemia
cancer of small b- lymphocytes associated with lymphocytosis (increased levels of WBCs)
where does CLL arise ?
arises in the bone marrow
what are the clinical features of chronic lymphocytic leukemia ?
lymphocytosis with or without lymphadenopathy
hepatosplenomegaly
bone marrow failure
what autoimmune diseases are associated with chronic lymphoid leukemia ?
immune thrombocytopenia , autoimmune haemolytic anemia
what is the difference between a lymphoma and leukemia ?
lymphoma arises from lymphoid organs ( spleen and lymph nodes
leukemia arises from the bone marrow
what are the clinical features of a lymphoma ?
lymph node enlargement
generally tired/unwell
weight loss
fever
what is the management for lymphomas ?
- full staging investigations
- broad categorisation on histology to asses aggressiveness
- chemotherapy, radiotherapy and monoclonal antibodies
how do non-hodgkin lymphomas arise ?
results from genetic events during antigen driven lymphocyte proliferation in peripheral lymphoid tissue
where do high grade lymphomas arise from (Burkitts lymphoma) ?
dark zone in secondary lymphoid organs
where do low grade lymphomas arise from ( follicular NHL)?
light zones in secondary lymphoid organs
what is the genetic translocation that occurs in burkitts lymphoma ?
t(8;14) IgH Myc
what is the genetic translocation that occurs in follicular NHL ?
t(14;18) IgH Bcl 2
what are the positive finding sin a low grade follicular NHL in immunochemistry ?
CD20 poositivity
what are the histological findings in hodgkin lymphoma ?
reed Sternberg cells
what do myelomas rise from ?
plasma cells
what is the common clinical presentation of multiple myelomas ?
fatigue/anemia bone pain/pathological fractures symptoms of hypercalcaemia symptoms of hyper viscosity renal failure
what is the treatment for multiple myeloma ?
chemotherapy
steroids
targeted agents (protesome inhibitors, thalidomide and analogues )
what are proteasome inhibitors ?
drugs that block the action of proteasome, cellular complexes that break down proteins
what is serum protein electrophoresis ?
used to identify patients with multiple myeloma and other serum protein disorders
what are the findings in SPEP in multiple myeloma patients ?
there will be a spike with gamma globulin proteins (M protein/myeloma protein)
how is a laboratory diagnosis made for multiple myeloma ?
microscopy - blood, BM aspirate and trephine
immunophenotyping - flow cytometry
cytogenetics - FISH analysis
molecular genetics - PCR
what are the typical antigens expressed by acute myeloid leukemia ?
CD33, 34, CD117, CD13 , cMPO
what would you find in a bone marrow smear of a chronic lymphoid leukemia patient ?
smudge cells ( easily smudge lymphocytes)
B cell CLL vs T cell CLL
95% are B cell lineages and T cell lineages have a worse prognosis
what are the surface markers of B cells ?
CD19
what is G banding ?
Giemsa banding is a technique used in cytogenetics to produce a visible karyotype by staining condensed chromosome
what techniques are used to asses for minimal residual disease in AML ?
RT-PCR
what is the genetic translocation in acute myeloid leukemia ?
t(15;17)
PML- RARA
