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Heme/Onc > Path > Flashcards

Path Flashcards

1
Q

B Symptoms

A

fever, night sweats, weight loss

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2
Q

Why are lymphoid cells common targets of genetic rearrangement? What can happen with rearrangement?

A 
Lymphoid cells make DNA breaks for recombination and class switching
Over-expression of normal protein, or creation of chimera with abnormal function
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3
Q

Why do most translocations occur with chromosome 14?

A 
Breaks occur here for class switching
Chromosomal translocation is behind a heavy chain promoter, which is very active
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4
Q

BCL6 function

A

Transcription repressor in germinal center

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5
Q

BCL2 function

A

BCL2 stabilizes mt membrane to prevent apoptosis

binds Bax/Bak to prevent pore formation (and therefore apoptosis)

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6
Q

BCL2 associated with…

A

Follicular B cell lymphoma (NHL)
t(14,18)
Mature lymphocyte population expands
Will see BCL2 in germinal centers (where it shouldn’t be…want apoptosis to occur here)
BCL2 stabilizes mt membrane to prevent apoptosis

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7
Q

C-MYC function

A

Transcriptional regulator of 1000s of genes

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8
Q

C-MYC associated with…

A 
Burkitt lymphoma (B-cell NHL)-100% of cases! 
t(8,14) 
Endemic: jaw or facial growth
Sporadic: abdomen 
Associated with HIV 
Starry sky appearance
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9
Q

Cyclin D1 function

A

Cell cycle checkpoint; between G1 and S

Phosphorylate Rb

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10
Q

Cyclin D1 associated with…

A

Mantle cell lymphoma
t(11,14)
Over-expression promotes G1–>S

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11
Q

BCL6 associated with

A

Diffuse B cell Lymphoma
t(3,14)
some problem with BCL6 occurs in 100% of DLBCL
Over-expression prevents cells from undergoing apoptosis in response to DNA damage (BCL6 is needed to repress transcription)

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12
Q

C-Abl function

A

Tyrosine kinase needed for a variety of processes needed for growth and survival

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13
Q

Bcr-Abl function and association

A

Balanced translocation creates a chimera responsible for CML, proliferation of granulocytes with the capacity to differentiate
t(9,22)
Constitutively active
Trapped in cytoplasm

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14
Q

Anaplastic lymphoma kinase (ALK) function

A

Non-receptor tyrosine kinase on chromosome 2

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15
Q

Anaplastic lymphoma kinase (ALK) associated with

A

Anaplastic Large Cell Lymphoma–type of T cell non-Hodgkin lymphoma
t(2,5) is most common translocation; creates chimera that results in constitutively active ALK

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16
Q

PML-RAR alpha fusion protein associated with

A

Acute Promyelocytic Leukemia
t(15,17) translocation creating a chimera that blocks retinoid acid receptor
Repression of transcription prevents cells from maturing
Treatment: All-trans retinoic acid (ATRA) to bypass the block

17
Q

RUNX1

A

Hematopoietic transcription factor

18
Q

RUNX1 translocations associated with

A

1) AML: t(8,21) loss of ability to regulate transcription; good prognostic indicator
2) ALL: t(12,21) loss of ability to regulate transcription; good prognostic indicator

19
Q

FLT3 function

A

Receptor tyrosine kinase needed for the development of cells and immune system
Binding of ligand signals proliferation

20
Q

FLT3 mutation associated with

A

AML
constitutive activation
poor prognosis

21
Q

JAK/STAT function and association

A 
non-receptor tyrosine kinase
Myeloproliferative disorders: mutation leads to constitutive activation
-Polycythemia Vera
-Essential thrombocytosis
-Primary myelofibrosis
22
Q

BRAF function

A

Small GTP binding protein associated with increased cell proliferation and survival

23
Q

BRAF mutation associated with…

A

Hairy Cell Leukemia (100% of cases), multiple myeloma, langerhan’s cell histiocytosis, and many others

24
Q

Notch

A

Transcriptional activator that regulates survival, differentiation, proliferation
Needed for hematopoiesis

25
Q

Notch mutation associated with…

A

50% T cell lymphoblastic leukemias

Mutations cause notch activation, therefore transcriptional activation

26
Q

Hydrops fetalis

A

Accumulation of fluid in two or more fetal compartments

Due to immune (hemolytic anemia of newborn) or non immune cases

27
Q

Cancers where B cells are CD5+

A

Chronic Lymphoid Leukemia

Mantle Cell Lymphoma

28
Q

Characteristics of Hodgkins Lymphoma

A

Cells originate from germinal B-cells, but do not express normal B cell marker. Express CD15+ and CD30+

Reed Sternberg cells release cytokines which attract other cells, making the mass look heterogenous

CD30+ causes constitutive activation of NFKB

Heme/Onc (2 decks)

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