Leucocytes Flashcards
Total leucocyte count reference range is:
4 – 11 x 109/L
What is the reference range for neutrophils, and what proportion of WBC do they constitute?
2 – 6.8 x 109/L (40 – 80%)
What is the reference range for lymphocytes, and what proportion of WBC do they constitute?
1 – 4 x 109/L (25 - 35%)
What is the reference range for monocytes, and what proportion of WBC do they constitute?
0.2 – 1.0 x 109/L (2 – 10%)
What is the reference range for eosinophils, and what proportion of WBC do they constitute?
0 – 0.5 x 109/L (0 – 5%)
What is the reference range for basophils, and what proportion of WBC do they constitute?
0 – 0.2 x 109/L (0 - 2%)
List two features of neutropaenia.
Highly motile cells and high risk of serious infections
True or false: neutrophilia is rarer than neutropaenia.
False
List three pathological causes of neutrophilia.
Acute infection, drugs, and acute haemorrhage
The ________ ___________ of neutrophils is thought to be due to impaired cytoplasmic maturation, in the effort to rapidly generate large numbers of granulocytes.
Toxic granulation
What are Döhle bodies?
Single or multiple blue cytoplasmic inclusions,
that are about 1-2µm long. They represent remnants of rough endoplasmic reticulum from earlier maturational stages. They are associated with myeloid ‘left shifts’, and are seen in conjunction with toxic granulation
The term ‘_________ ________’ applies to chronic neutrophilia with marked leucocytosis (>25 x 109/L).
Leukaemoid reaction
A ______________ picture indicates severe disruption of the marrow, and is common in myelofibrosis (primary or secondary).
Leucoerythroblastic
_________ _________ anomaly is an autosomal dominant disorder whereby granulocyte nuclei fail to segment normally. Most granulocytes have bi-lobed nuclei, resembling bands. Cell function is normal. An acquired or ‘pseudo-Pelger-Huët’ anomaly is seen in myelodysplastic disorders and following drug therapy, and may accompany leukaemia and certain infections. Chromatin shows intense clumping, to help differentiate these cells from myelocytes,
Pelger-Huët
_______________ is usually observed in allergic disorders or parasitic infection, or in asthma, eczema, drug treatment.
Eosinophilia
___________ may result from viral, fungal, rickettsial, and protozoal infections.
Monocytosis
______________ occurs most frequently during viral infections and only rarely in bacterial infection, except Bordatella pertusis.
Lymphocytosis
Collectively, haematological malignancies account for approximately ___% of all cancers, with a considerably higher (greater than threefold) proportion of childhood cancers.
8
_____________ anaemia is a mutation in the FA genes that normally helps repair DNA damage.
Fanconi’s
Wiscott-Aldrich Syndrome involves mutations in the WAS gene, which affects the ability of _______ _______ to relay signals from the surface to the cytoskeleton.
Blood cells
True or false: radiation is leukaemogenic.
True
__________ involve ‘gain-of-function’ mutations.
Oncogenes
_______-__________ are involved in a variety of important cellular processes e.g., cell-signalling pathways, directing cellular growth, differentiation and proliferation.
Proto-oncogenes
Tumour-suppressor genes cause ‘loss-of-function’ _____________.
Mutations
________ is a protein that interacts signalling pathways involved with cycle arrest, DNA repair, and apoptosis.
p53
The term ‘aneuploid’ refers to:
Abnormal (odd) number of chromosomes, not a multiple of 23.
__________ alterations (does not affect DNA sequence but results in a change in gene expression, e.g., methylation).
Epigenetic
___________ play a role in regulating gene expression.
MicroRNAs
______________ chromosome, t(9;22) BCR/ABL, is associated with CML.
Philadelphia
t(15;17), retinoic acid receptor is associated with _______ _________ __________
Acute myeloid leukaemia
MicroRNAs _____________ gene expression.
Downregulate
_____________ stains granules of granulocytes.
Myeloperoxidase
Sudan Black B stains _______ in granules.
Lipids
_________ ______ ________ stains glycogen.
Periodic Acid Schiff
Acid phosphatase - shows characterising staining in __-_____.
T-ALL
In _______ _________ _________, the cells can be identified by using antibodies directed against markers, such as CD13, CD117, etc..
Acute myeloid leukaemia
____________ __-_______ ______________ detects extra copies of genetic material.
Fluorescent in-situ hybridisation
True or false: acute leukaemia often goes into remission, but may have a relapse.
True
__________ leukaemia is an aggressive disease, with predominantly blast cells, some mature forms, and very few intermediate stage cells.
Acute
Chronic leukaemia is less aggressive, with a predominance of more __________ cells, with <20% blasts.
Mature
Acute leukaemia (AL) is defined as the presence of >20% __________ in the blood or bone marrow.
Blasts
The classic triad of leukaemia is anaemia, ______________ and bleeding due to reduced levels of normal blood cells.
Infection
List the three main forms of B-lymphoblastic leukaemia.
B-lymphoblastic leukaemia/lymphoma with translocations( t(9;22)(q34;q11.2); BCR-ABL 1)
B-lymphoblastic leukaemia/lymphoma with hyperdiploidy
B-lymphoblastic leukaemia/lymphoma with hypodiploidy
List three clinical features of leukaemia.
Bone marrow failure, neutropaenia, and thrombocytopaenia
True or false: normochromic-normocytic anaemia is often observed in acute leukaemia.
True
List the main forms of AML.
AML with recurrent genetic abnormalities
APL with t(15,17) (q22;q12); PML-RARA (acute promyelocytic leukaemia)
AML with myelodysplasia-related changes (significant dysplasia)
AML, therapy related (previous chemotherapy)
AML, not otherwise specified is categorised according to morphology, cytochemistry and immunophenotype (old FAB classification) (no common genetic abnormalities)
AML with minimal differentiation (no granules in cytoplasm of blasts)
AML without maturation (mostly myeloblasts (Auer rods))
Acute myelomonocytic leukaemia (increase in immature neutrophils and monocytes in the bone marrow)
Acute monoblastic/monocytic leukaemia (increase in immature monocytes)
Acute erythroid leukaemia (immature cells of the erythroid lineage present)
Acute megakaryoblastic leukaemia (abnormal megakaryoblasts)
What are some clinical features of CML?
Bruising, epistaxis, and splenomegaly
True or false: leucocytosis and increased basophils are characteristic of CML.
True
CML bone marrow studies will be hypercellular, with a predominance of ___________ cells.
Myeloid
CML will have a low leucocyte ___________ ____________ score.
Alkaline phosphatase
CML will, in terms of molecular biology, be Ph chromosome-positive or BCR/____-positive.
ABL
True or false: CML will never convert to AML.
False
_____________ syndromes are serious and relatively common; they are most common in the elderly population.
Myelodysplastic
List the five main types of myelodysplastic syndrome.
MDS with single lineage dysplasia
MDS with ring sideroblasts (MDS-RS)
MDS with multilineage dysplasia
MDS with excess blasts
MDS with isolated del(5q)
What is the scientific term for a reduction in one or more cell lines?
Cytopaenia
In some myelodysplastic syndrome varients, ring ____________ are seen in the bone marrow, due to presence of iron-loaded mitochondria.
Sideroblasts
Giant, ______________ platelets are often observed in myelodysplastic syndromes.
Hypogranular
In myelodysplastic syndromes, usually a macrocytic, sometimes ____________, picture is observed.
Dimorphic
Anisocytosis, poikilocytosis, _____________ stippling, Howell-Jolly bodies, and NRBC may be observed in myelodysplastic syndrome.
Basophilic
True or false: there is considerable overlap between leukaemias and lymphomas.
True
List the two most common variants of lymphoma.
Hodgkin’s and non-Hodgkin’s
B-cell __________ correspond to stages of maturation.
Neoplasms
Pre-cursor B cells that are produced and mature in the bone marrow may undergo ___________, or develop into mature B cell.
Apoptosis
B cells that have acquired a mutation give rise to B cell ________________ _____________.
Lymphoblastic leukaemia
Upon encountering ___________, B lymphocytes undergo blast transformation in the lymph nodes to form effector lymphocytes.
Antigen
B cells may acquire abnormality while proliferating in the __________ _____-.
Mantle zone
B cells may enter the ____________ _________, where somatic hypermutations occur (GC neoplasms), and they switch from coding polyreactive antibodies into clones that express specific antibodies.
Germinal centres
List two types of post-germinal centre cells.
Plasma cells and memory B cells
True or false: chronic lymphocytic leukaemia is not a post-germinal centre neoplasm.
False
T cell progenitors leave the bone marrow and enter the thymus where they develop into ________naïve T cells.
Naïve
If an abnormality is acquired in either the bone marrow or ___________, T lymphoblastic leukaemia/lymphoma may develop.
Thymus
When T cells leave the thymus and encounter antigen they undergo ________ ______________, and develop into memory and effector T cells.
Blast transformation
If an abnormality is acquired in ____________ ____________ ________, there may be peripheral (mature) T cell lymphoma/leukaemia.
Peripheral lymphoid tissue
List two forms of neoplasms, other than Hodgkin’s lymphoma.
Precursor T cell neoplasm and mature T cell neoplasm
Give three mature B cell neoplasms.
B cell prolymphocytic leukaemia
Hairy cell leukaemia
Plasma cell myeloma
B cell chronic lymphocytic leukaemia (CLL) has a peak incidence in what age group?
60-80 years
List three aetiological features of B cell chronic lymphocytic leukaemia.
Familial association, prolonged lifespan of B cells, and impaired apoptosis
In B-CLL, failure of apoptosis is associated with _________________ of a known suppressor of apoptosis.
Upregulation
State three clinical features of B-CLL.
Features of anaemia, thrombocytopaenia, and neutropaenia, lymphadenopathy, and immunosuppression
Lymphocytosis (>5 x 109 /l, up to 300 x 109 /l), N/N anaemia (may develop due to autoimmune haemolysis), and thrombocytopaenia are laboratory findings of which neoplasm?
B cell chronic lymphocytic leukaemia
List three feature that might be seen on a B-CLL blood film.
Smudge cells, less than 20% blasts, and inconspicuous nucleoli
List two features of B-CLL immunophenotyping
B cells will have surface CD19+
Weak expression of surface IgM or IgD (monoclonal)
_________________ replacement of normal marrow may be observed on in the bone marrow in B-CLL.
LymphocytiC
True or false: translocations and trisomies, but not deletions, are seen in B-CLL.
False
In B-CLL, immunoglobulin will have ____________ concentration, and will be more marked with advanced disease.
Reduced
List three forms of treatment for B-CLL.
Immunochemotherapy (biological therapy), such as antiCD20 (Rituximab), chemotherapy, and radiation
Malignant cells accumulate in lymph nodes, in a phenomenon known as _____________________.
Lymphadenopathy
The ______________ _______ occurs when malignant cells spill over into the blood.
Leukaemic phase
What is Hodgkin’s lymphoma characterised by?
Presence of Reed-Sternberg (RS) cells
True or false: Hodgkin’s lymphoma arises from T cells.
False
With what previous infection is Hodgkin’s lymphoma associated?
Epstein-Barr virus, and particularly infectious mononucleosis
Hodgkin’s lymphoma has a ______ cure rate.
High
Non-Hodgkin’s lymphoma is usually derived from ___ cells.
B
True or false: the aetiology of non-Hodgkin’s lymphoma is poorly understood.
True
______________ reflects the synthesis of Ig from a single clone of plasma cells, and is sometimes non-malignant.
Paraproteinaemia
Paraproteinaemia is characterised by a _____________ immunoglobulin (Ig) band in the serum.
Monoclonal
Define multiple myeloma.
Neoplastic proliferation of lymphocytes (B cells)
Give three characteristics of multiple myeloma.
Accumulation of plasma cells in the bone marrow
Presence of monoclonal protein in the serum
Related organ or tissue damage (bone pain is a common presenting feature)
Giant _____________ platelets, with functional problems, are observed is myelodysplastic syndrome.
Hypogranular
