Intro To Leukemia

Question 1

What are Leukaemias?

Answer 1

Malignant neoplasm of the white blood cell, characterized by involvement of the bone marrow and blood

Question 2

Leukaemias?

A group of disorders characterized by the _________ of __________ in the ________ and _______

Answer 2

accumulation

malignant white cells

bone marrow and blood.

Question 3

Leukaemias?

(Localized or Generalized?) _______ proliferations or accumulation of leukopoietic cells with or without involvement of the ______

Answer 3

Generalized

neoplastic

peripheral blood

Question 4

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 _____________

Answer 4

any

developmental stage affected

Question 5

LEUKAEMIA AETIOLOGY PRINCIPLES

The neoplastic cell is a ___________ cell, or a ___________ cell - lymphoid or myeloid commitment.

Answer 5

hematopoietic pleuripotent stem

committed stem

Question 6

LEUKAEMIA AETIOLOGY PRINCIPLES

Leukemogenesis is characterized by dysregulation of ______,_______, or _____, associated with _________ and then proliferation of the leukemic clone.

Answer 6

cell growth, differentiation or death

genetic mutations

Question 7

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

Answer 7

differentiation

blasts

death

matured

Question 8

LEUKAEMIA AETIOLOGY PRINCIPLES
The TWO-HIT MODEL OF LEUKEMOGENESIS

posits that acute leukemias arise from _______ derangements of _____ that regulate hematopoietic _______ and _____

Answer 8

two (or more)

genes

differentiation and proliferation.

Question 9

One mutation alone is sufficient to generate the acute leukaemia phenotype.

T/F

Answer 9

F

Question 10

Two-hit model of leukemogenesis

_____ of function of transcription factors needed for ________

____ of function mutations of tyrosine kinases

Answer 10

Loss ; differentiation

Gain

Question 11

Two-hit model of leukemogenesis

_________ + __________ = Acute Leukemia

Answer 11

Differentiation block

Enhanced proliferation

Question 12

LEUKAEMIA AETIOLOGY
No known causes of leukaemia but certain factors are associated with the aetiology.
A combination of

_______ background (______ alterations)

_____ factors

________ influence

Answer 12

Genetic; Chromosomal

Host

Environmental

Question 13

Causes of LEUKAEMIA AETIOLOGY

List 4

Answer 13

No known causes of leukaemia

Question 14

LEUKAEMIA AETIOLOGY: Chromosomal alterations

• growth promoting ______

•growth inhibiting _______

genes that regulate __________

Answer 14

oncogenes

tumour suppressor genes

programmed cell death or apoptosis -

Question 15

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 _________

Answer 15

cell proliferation

Brake; proliferation

cell proliferation.

Question 16

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 ______.

Answer 16

subtle

large enough

karyotype

Question 17

LEUKAEMIA AETIOLOGY

The common types of structural abnormalities in tumour cells are:

_______
_______
__________
___________

Answer 17

Translocation
Point mutation
Deletion
Gene amplification

Question 18

LEUKAEMIA AETIOLOGY

Whole chromosomes may be gained or lost

T/F

Answer 18

T

Question 19

Translocations are rare in haemopoietic neoplasms.

T/F

Answer 19

F

extremely common

Question 20

LEUKAEMIA AETIOLOGY
Most notable Translocations is ________ in _______ .

Answer 20

Philadephia (Ph1) in CML

Question 21

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 ____.

Answer 21

9

22

reciprocal translocation

90

CML

Question 22

LEUKAEMIA AETIOLOGY

Point Mutation: eg Mutation within the ____ oncogene

Answer 22

RAS

Question 23

LEUKAEMIA AETIOLOGY

________ of are the second most prevalent abnormality in tumour cells.

Answer 23

Deletions

Question 24

LEUKAEMIA AETIOLOGY

Deletion of chromosome ____ is the most common chromosomal abnormality in polycythaemia _____.

Answer 24

20q

rubra vera

Question 25

LEUKAEMIA AETIOLOGY Gene Amplification is the process by which the ________ of a chromosome segment is increased in a somatic cell.

Answer 25

number of copies

Question 26

LEUKAEMIA AETIOLOGY __________ is very rare in haematologic malignancy.

Answer 26

Gene Amplification

Question 27

Haemopoietic Stem Cell Mutations increase with age T/F

Answer 27

T

Question 28

LEUKAEMIA AETIOLOGY : Host Factors i. Heredity: Heredity plays an important role in leukaemias. Identical twins (have ____% chance), Fraternal twins have (more or less?) chance

Answer 28

25 Less

Question 29

LEUKAEMIA AETIOLOGY : Host Factors i. _______ ii. _________ abnormalities iii.__________ iv. Chronic ________

Answer 29

Heredity Congenital chromosomal Immunodeficiency Marrow dysfunction

Question 30

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

Answer 30

Higher 40; incr Klinefelter; turner; fanconi; bloom

Question 31

LEUKAEMIA AETIOLOGY : Host Factors Immunodeficiency: Anything that disturbs the _______ may lead to development of leukaemias because the protection has been removed.

Answer 31

immune surveillance

Question 32

LEUKAEMIA AETIOLOGY : Host Factors Chronic Marrow dysfunction e.g. __________, clonal blood disorder such as ________ and _____

Answer 32

Myelodysplastic syndrome (MDS) aplastic anaemia & PNH.

Question 33

LEUKAEMIA AETIOLOGY Hematologic disorders predisposing to acute leukemia _____ and other myeloproliferative disorders (PRV, ET, MF) _______ syndromes ______ anaemia

Answer 33

CML Myelodysplastic Aplastic

Question 34

LEUKAEMIA AETIOLOGY Hematologic disorders predisposing to acute leukemia Multiple myeloma: ______________________ ________________________(PNH)

Answer 34

Waldenström’s macroglobulinaemia Paroxysmal Nocturnal Haemoglobinuria

Question 35

Acute leukaemia arising out of hematologic disorders is more frequently _______ than ______

Answer 35

AML than ALL

Question 36

LEUKAEMIA AETIOLOGY :Environmental Factors ________ _________ _________

Answer 36

Ionizing radiations Chemicals & drugs Viruses

Question 37

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.

Answer 37

Radiotherapy, X-ray foetus Atomic bombs

Question 38

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.

Answer 38

Busulphan, chlorambucil Benzene; petroleum

Question 39

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.

Answer 39

retro; C Reverse transcriptase

Question 40

HTLV-1 - Human T cell Leukemia/Lymphoma Virus can cause _______ but not _______

Answer 40

T-cell ALL but not AML

Question 41

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 _____

Answer 41

Acute and Chronic leukaemia Myeloid and Lymphoid

Question 42

Differentiate between avute and chronic leukemia under the following Onset Cell type Survival Treatment

Answer 42

Rapid ; Gradual Blast cells; mature Commonly fatal ; Long survival Ammenable to chemotherapy ; may be resistant

Question 43

In ACUTE LEUKAEMIAS There is usually: increased __________ reduced ________ block in ____________

Answer 43

rate of proliferation apoptosis cellular differentiation.

Question 44

CHRONIC LEUKAEMIAS Excessive build up of relatively _____, but still _______ white blood cells. Typically take _____ or______ to progress

Answer 44

mature abnormal months or years

Question 45

CHRONIC LEUKAEMIAS Chronic leukaemias are sometimes _______ before treatment to ensure _____________.

Answer 45

monitored for some time maximum effectiveness of therapy

Question 46

Chronic leukemia mostly occurs in (younger or older?) people.

Answer 46

Older