Intro To Leukemia Flashcards
What are Leukaemias?
Malignant neoplasm of the white blood cell, characterized by involvement of the bone marrow and blood
Leukaemias?
A group of disorders characterized by the _________ of __________ in the ________ and _______
accumulation
malignant white cells
bone marrow and blood.
Leukaemias?
(Localized or Generalized?) _______ proliferations or accumulation of leukopoietic cells with or without involvement of the ______
Generalized
neoplastic
peripheral blood
Recall normal haemopoiesis -
Abnormality can occur at _____ stage in the maturation sequence and lead to a variety of leukaemic illnesses which are classified according to the _____________
any
developmental stage affected
LEUKAEMIA AETIOLOGY PRINCIPLES
The neoplastic cell is a ___________ cell, or a ___________ cell - lymphoid or myeloid commitment.
hematopoietic pleuripotent stem
committed stem
LEUKAEMIA AETIOLOGY PRINCIPLES
Leukemogenesis is characterized by dysregulation of ______,_______, or _____, associated with _________ and then proliferation of the leukemic clone.
cell growth, differentiation or death
genetic mutations
LEUKAEMIA AETIOLOGY PRINCIPLES
When _______ is blocked at an early stage, leads to accumulation of _____ and the clinical consequences.
And with Cell _____ blocked – accumulation of _____ cells
differentiation
blasts
death
matured
LEUKAEMIA AETIOLOGY PRINCIPLES
The TWO-HIT MODEL OF LEUKEMOGENESIS
posits that acute leukemias arise from _______ derangements of _____ that regulate hematopoietic _______ and _____
two (or more)
genes
differentiation and proliferation.
One mutation alone is sufficient to generate the acute leukaemia phenotype.
T/F
F
Two-hit model of leukemogenesis
_____ of function of transcription factors needed for ________
____ of function mutations of tyrosine kinases
Loss ; differentiation
Gain
Two-hit model of leukemogenesis
_________ + __________ = Acute Leukemia
Differentiation block
Enhanced proliferation
LEUKAEMIA AETIOLOGY
No known causes of leukaemia but certain factors are associated with the aetiology.
A combination of
_______ background (______ alterations)
_____ factors
________ influence
Genetic; Chromosomal
Host
Environmental
Causes of LEUKAEMIA AETIOLOGY
List 4
No known causes of leukaemia
LEUKAEMIA AETIOLOGY: Chromosomal alterations
• growth promoting ______
•growth inhibiting _______
genes that regulate __________
oncogenes
tumour suppressor genes
programmed cell death or apoptosis -
LEUKAEMIA AETIOLOGY : Chromosomal alterations:
growth promoting oncogenes - mutation leads to abnormal ________
growth inhibiting tumour suppressor genes - mutation removes the molecular ____ leading to uncontrolled ______
genes that regulate programmed cell death or apoptosis - mutation causes excessive _________
cell proliferation
Brake; proliferation
cell proliferation.
LEUKAEMIA AETIOLOGY
The genetic damage that activates oncogenes or inactivates tumour suppressor genes may be _____ (e.g point mutation) or _______ to be detected in a ______.
subtle
large enough
karyotype
LEUKAEMIA AETIOLOGY
The common types of structural abnormalities in tumour cells are:
_______
_______
__________
___________
Translocation
Point mutation
Deletion
Gene amplification
LEUKAEMIA AETIOLOGY
Whole chromosomes may be gained or lost
T/F
T
Translocations are rare in haemopoietic neoplasms.
T/F
F
extremely common
LEUKAEMIA AETIOLOGY
Most notable Translocations is ________ in _______ .
Philadephia (Ph1) in CML
LEUKAEMIA AETIOLOGY
In Philadelphia chromosome, part of chromosome _____ is transferred to chromosome _____ and vice versa hence there is ________ between both chromosomes which results in leukaemia. This cytogenetic change is seen in ____% of cases of ____.
9
22
reciprocal translocation
90
CML
LEUKAEMIA AETIOLOGY
Point Mutation: eg Mutation within the ____ oncogene
RAS
LEUKAEMIA AETIOLOGY
________ of are the second most prevalent abnormality in tumour cells.
Deletions
LEUKAEMIA AETIOLOGY
Deletion of chromosome ____ is the most common chromosomal abnormality in polycythaemia _____.
20q
rubra vera
LEUKAEMIA AETIOLOGY
Gene Amplification is the process by which the ________ of a chromosome segment is increased in a somatic cell.
number of copies
LEUKAEMIA AETIOLOGY
__________ is very rare in haematologic malignancy.
Gene Amplification
Haemopoietic Stem Cell Mutations increase with age
T/F
T
LEUKAEMIA AETIOLOGY : Host Factors
i. Heredity: Heredity plays an important role in leukaemias. Identical twins (have ____% chance), Fraternal twins have (more or less?) chance
25
Less
LEUKAEMIA AETIOLOGY : Host Factors
i. _______
ii. _________ abnormalities
iii.__________
iv. Chronic ________
Heredity
Congenital chromosomal
Immunodeficiency
Marrow dysfunction
LEUKAEMIA AETIOLOGY : Host Factors
Congenital chromosomal abnormalities: Patients with these illnesses have (higher or lower?) chance of having acute leukaemias.
Down’s Syndrome –___% chance of AML, ___eased incidence of ALL
______ syndrome
______ Syndrome
______ anaemia
______ Syndrome
Higher
40; incr
Klinefelter; turner; fanconi; bloom
LEUKAEMIA AETIOLOGY : Host Factors
Immunodeficiency: Anything that disturbs the _______ may lead to development of leukaemias because the protection has been removed.
immune surveillance
LEUKAEMIA AETIOLOGY : Host Factors
Chronic Marrow dysfunction e.g. __________, clonal blood disorder such as ________ and _____
Myelodysplastic syndrome (MDS)
aplastic anaemia & PNH.
LEUKAEMIA AETIOLOGY
Hematologic disorders predisposing to acute leukemia
_____ and other myeloproliferative disorders (PRV, ET, MF)
_______ syndromes
______ anaemia
CML
Myelodysplastic
Aplastic
LEUKAEMIA AETIOLOGY
Hematologic disorders predisposing to acute leukemia
Multiple myeloma: ______________________
________________________(PNH)
Waldenström’s macroglobulinaemia
Paroxysmal Nocturnal Haemoglobinuria
Acute leukaemia arising out of hematologic disorders is more frequently _______ than ______
AML than ALL
LEUKAEMIA AETIOLOGY :Environmental Factors
________
_________
_________
Ionizing radiations
Chemicals & drugs
Viruses
LEUKAEMIA AETIOLOGY 3Environmental Factors
Ionizing radiations – Malignancy may develop following repeated exposure to heavy ionising radiations
e.g. _____,_____
e.g. in a pregnant woman – leukaemia may develop in the ____.
So also are victims of ______ who later developed leukaemia.
Radiotherapy, X-ray
foetus
Atomic bombs
LEUKAEMIA AETIOLOGY :Environmental Factors
Chemicals & drugs – Certain drugs are known to predispose to secondary malignancies like leukaemias.
Some of these drugs are used to treat malignancy e.g. ______,______which are alkylating agents.
Certain chemicals e.g. ____ containing chemicals like _____ products have also been implicated.
Busulphan, chlorambucil
Benzene; petroleum
LEUKAEMIA AETIOLOGY: Environmental factors
Viruses: – Can directly cause leukaemias. It is now known that the _____viruses especially the ___-type RNA viruses can cause leukaemias. These viruses possess the ________ enzyme.
retro; C
Reverse transcriptase
HTLV-1 - Human T cell Leukemia/Lymphoma Virus can cause _______ but not _______
T-cell ALL but not AML
LEUKAEMIA CLASSIFICATION
Main classification is into 2 groups based on the stage of cell maturation at which the abnormalities occur: _______ and ________
Each group is subdivided into 2 based on the lineage of cells affected: ______ and _____
Acute and Chronic leukaemia
Myeloid and Lymphoid
Differentiate between avute and chronic leukemia under the following
Onset
Cell type
Survival
Treatment
Rapid ; Gradual
Blast cells; mature
Commonly fatal ; Long survival
Ammenable to chemotherapy ; may be resistant
In ACUTE LEUKAEMIAS
There is usually:
increased __________
reduced ________
block in ____________
rate of proliferation
apoptosis
cellular differentiation.
CHRONIC LEUKAEMIAS
Excessive build up of relatively _____, but still _______ white blood cells.
Typically take _____ or______ to progress
mature
abnormal
months or years
CHRONIC LEUKAEMIAS
Chronic leukaemias are sometimes _______ before treatment to ensure _____________.
monitored for some time
maximum effectiveness of therapy
Chronic leukemia mostly occurs in (younger or older?) people.
Older
