Acute Leukemia Flashcards
(94 cards)
1
Q
White Cell Neoplasms (3)
A
- based on origin and differentiation
1. lymphoid neoplasms
2. myeloid neoplasms
3. histocytic neoplasms
2
Q
Lymphoid Neoplasms
A
-certain leukemias
-Hodgkin
- non-Hodgkin
plasma cell dyscrasis
3
Q
Myeloid Neoplasms
A
- certain leukemias
- myelodysplastic sydromes (MDS)
- myeloproliferative neoplasms
4
Q
Histocytic Neoplasms
A
- Langerhans
- histiocytoses
5
Q
Lymphoid neoplasms characteristically manifest as _________, w/ involvement of _________ and ________
A
- leukemias
- bone marrow and peripheral blood
6
Q
Lymphomas present in _____
A
lymph nodes or other tissues
7
Q
Plasma cell tumors manifest as
A
discrete masses
8
Q
All lymphoid neoplasms have the potential to spread to lymph nodes and other tissues– especially the liver, spleen, bone marrow, and peripheral blood.
A
yep
9
Q
B and T cell tumors are composed of
A
cells arrested at or derived from a specific stage of normal lymphocyte differentiation
10
Q
1st progenitor in normal lymphopoiesis is
A
lymphoblast
11
Q
WHO classifies lymphoid neoplasms on (4)
A
- morphology
- cell of origin
- genotype
- clinical features
12
Q
Acute Lymphoid Leukemias/Lymphomas/ALLsare comprised of
A
immature B(pre-B) or T(pre-T) cells aka lymyphoblasts
13
Q
Most ALLs are_________ and manifest as childhood acute leukemias.
A
B-ALLs
14
Q
Less common ALLs are ________ and manifest in adolescent males as thymic lymphomas.
A
T-ALLs
15
Q
ALL is most common cause of cancer of _________
A
children
- 2500 new cases per year–> mostly in kids under 15
- 3x more common in whites
- males>females
- Hispanics have highest incidence
16
Q
B-ALL peaks at around _____
A
age 3
17
Q
T-ALL is in adolescence b/c this is when _______________
A
the thymus reaches max size
18
Q
chromosomal lesions in ALL _______ the expression and fxn of __________ needed for normal differentiation of B/T cell progenitors
A
- dysregulate
- transcription factors
19
Q
up to 70% of T-ALLs are ________mutations in ____ that is essential in T cell differentiation
A
- gain-of-function
- NOTCH1
20
Q
Lots of B-ALLs have _____________ mutations in genes required for B cell differentiation.
A
- loss-of-function
- Eg. PAX5
21
Q
Varied mutations in T-/B-ALLs __________________
A
promote maturation arrest and increased self-renewal –> seen in immortalized cells
22
Q
Mutations in genes are NOT sufficient to produce ALL
A
preach
23
Q
Lesions that drive cell growth –> mutations that increase tyrosine kinase activity and RAS signaling are what?
A
also seen in ALL
24
Q
what does a bone marrow look like in ALL?
A
hypercellular and packed with lymphoblasts
25
Mediastinal masses occur in 50-70% in _______ which are more likely to be associated with ___________`
- T-ALLs
| - lymphdenopathy and splenomegaly
26
ALL is _______ (another word for really bad)
aggressive
27
What is one reason ALL is so aggressive?
high mitotic rate
28
B-/T-ALLs --> histo
- scant basophilic cytoplasm
- nuclei w/ delicate/fine;y stipple chromatin
- small nuclei
29
Appearance of blasts is identical in Pre-B/Pre-T ALLs
can't rule out other AML just based on this
| -DX RELIES ON IMMUNOPHENOGENIC STUDIES
30
Peripheral blood findings are ___________
highly variable
31
WBC can be ____________ or __________
high = over 100,000 OR low = under 10,000
32
some pt with ALL might have no circulating blasts =
aleukemic leukemia
33
ALL - 3 common peripheral blood findings
- anemia
- low platelet count below 100,000
- neutropenia
34
_____% of ALLs have ______________abnormalities
- 90
| - karyotypic
35
Childhood pre-B cell tumors are ______ AND have a _______ translocation involving the ETV6 and RUNX1 genes
- hyperdiploidy
- (12:21)
- creates a fusion gene encoding an aberrant transcription factor
36
ABL and BCR translocation
t(9:22) -- in 25% of adult pre-C cell tumors
37
Pre-T cell tumors have __________
diverse chromosomal changes
38
Terminal deoxynucleotidyl transferase (TdT)
enzyme specifically expressed in pre-B and pre-T cells --> present in more than 95% cases
39
ALL B-cell markers
TdT+ and CD19+
40
ALL T-cell markers
TdT+ and CD2
41
Most pts present w/n a few weeks of the onset of symptoms
yep
42
ALL Clinical Features: Related to Depression of Marrow Function (4)
- fatigue resulting from anemia
- fever
- reflecting infections secondary to neutropenia
- bleeding due to thrombocytopenia
43
ALL Clinical Features: Caused by Neoplastic Infiltration (4)
- generalized lymphadenopathy
- splenomegaly
- hepatomegaly
- complications related to compression of large vessels and areas in mediastinum (T-ALL only)
44
ALL Clinical Features: CNS Manifestations (4)
- result from meningeal spread
- headache
- vomiting
- nerve palsies
45
In children, what is the outlook? (ALL)
95% obtain remission and 75-85% are cured
46
ALL is the ____________________ in children.
the leading cause of cancer deaths
47
In adults, what is the outlook? (ALL)
35-40% cured
48
4 Factors associated with WORSE prognosis (ALL)
- younger than 2 yr
- adolescence/adulthood
- peripheral blood blast counts greater than 100,000
- detection of residual disease AFTER therapy
49
3 Factors associated with a FAVORABLE prognosis (ALL)
- 2-10yr
- low white cell count
- hyperdiploidy
50
Treatment of BCR-ABL (9;22)
BCR-ABL kinase inhibitors in combo with chemo
51
Why is the outlook for adults with ALL guarded?
adults cannot tolerate the intensive chemo that is curative in kids
52
Key Concept: ALL are highly aggressive tumors that manifest with signs and symptoms of ____________________ or as ___________
- bone marrow failure
| - rapidly growing masses
53
Key Concept: In ALL, tumor cells contain genetic lesions that ______________, leading to the accumulation of _______________
- block differentiation
| - immature, nonfunctional blasts
54
Granulopoiesis
synthesis of azurophilic granules and specific granules in the cytoplasm
55
Myeloblast
most immature of the myeloid series
56
Promyelocyte
basophilic cytoplasm and azurophilic granules containing lysosomal enzymes
57
Myelocyte
specific granules appear
58
Metamyelocyte
increasing number of specific granules
59
Band Cell
nucleus but not yet polymorphic
60
Segmented granulocytes
maturation
61
Myeloid Neoplasms arise from _____________ and give rise to _____________
- hematopoietic progenitors
| - proliferation that involve the bone marrow and replace normal marrow elements
62
Myeloid Neoplasia: Acute Myeloid Leukemia (AML)
- neoplastic cells are BLOCKED at an early stage
| - immature myeloblasts accumulate in marrow, replace normal elements, and circulate peripheral blood
63
Myeloid Neoplasia: Myelodysplastic Syndrome (MDS)
-terminal differentiation occurs in a DISORDERED and INEFFECTIVE way ---> dysplastic marrow precursors and peripheral blood cytopenias
64
Myeloid Neoplasia: Myeloproliferative Neoplasms
- neoplastic clones continues to undergo terminal differentiation but exhibits INCREASED OR DYSREGULATED GROWTH
- increase in one or more of the formed elements in the peripheral blood
65
AML primarily affects_______ and the median age is
- older adults
| - 50 years
66
AML symptoms are usually related to __________________
the replacement of normal marrow elements by leukemic blasts
67
AML: symptoms (5) - present w/n a few weeks of onset of symptoms
- fatigue
- pallor
- abnormal bleeding
- infections
- granulocytic sarcoma (manifesting in discrete tissue mass)
68
AMLs harbor mutations ___________
in transcription factors
- interfere with the differentiation of early myeloid cells---> leading to the accumulation of myueloid precursors in the marrow
69
AML subset: Acute Promyelocytic Leukemia (APL): Mutation
t(15;17)
-fusion of the retinoic acid receptor alpha (RARA) gene on chromosome 17 and the PML gene on chromosome 15 = PML/RARA fusion protein blocks myeloid differentiation at the promyelocytic stage
70
AML subset: APL: Treatment
all-trans retinoic acid (ATRA) = analogue of vitamin of A---> induces the neoplastic promyelocytes to differentiate into neutrophils
-rapid clearance of tumor
71
AML, what does the bone marrow look like?
AML myeloid blasts or promyelocytes make up more than 20% of the marrow
72
Auer Rods
red staining rod-like structures in myeloblasts or more differentiated cells
--MORE numerous in APL
73
In some subtypes of AML _______, _____________, and ____________ predominate
- monoblasts
- erythroblasts
- megakaryocytes
74
AMLs are DIVERSE in terms of ... (3)
- genetics
- cellular lineage
- degree of mutation
75
WHO classification of AML (4)
- specific genetic aberrations
- dysplasia
- occurring after genotoxic chemo
- lacking any of the above--> these are further subclassified
76
AML: FAB Classification also exists honestly idk if we had to know if but like its just progressively worse from M0 to M7
eh
77
AML: Immunophenotype
CD13, CD14, CD15, CD33, CD64, CD117(KIT)
| - CD34 present on myeloblasts
78
AML: Clinical Features: Symptoms (6)
- anemia
- neutropenia
- thrombocytopenia
- fatigue
- fever
- spontaneous mucosal and cutaneous bleeding
79
AML: Clinical Features: Thrombocytopenia
- results in bleeding disorder w/ cutaneous petechiae and eccymoses, serosal hemorrhages, and mucosal hemorrhages
- procoagulants and fibrinolytic factors released by leukemic cells EXACERBATE BLEEDING TENDNCY---> DIC
80
AML: Clinical Features: Infections
- frequent
| - caused by OPPORTUNISTS
81
AML: Clinical Features: CNS
CNS less common than ALL
82
AML: Clinical Features: Tumors with "Good-Risk" Karyotypic Abnormalitites
- t(8;21) and inv(16)
| - 50% long-term disease-free survival but OVERALL survival in all pt is 15-30%
83
AML: Clinical Features: TP53 Mutations
particularly poor prognosis
84
Myelodysplastic Syndrome (MDS)
clonal stem cell disorders characterized by maturation defects associated with INEFFECTIVE hematopoiesis and HIGH RISK OF TRANSFORMATION to AML
85
MDS: bone marrow
-hypercellular and normocellular
partly or wholly replaced by clonal progeny of transformed multipotent stem cell that retains the capacity to differentiate into RBCs, granulocytes, and platelets but in a manner that is both INEFFECTIVE AND DISORDERED
86
MDS: peripheral blood
-one or more cytopenias
87
MDS: stem cell clone
genetically unstable and prone to acquisition of additional mutations and the eventual transformation to AML
-most cases are IDIOPATHIC
88
MDS: Mutated Gene Categories (3)
- epigenetic factors
- RNA splicing factors
- transcription factors
- some have loss-of-function mutations in TP53=tumor suppressor gene--> these correlate with complex karyotype and poor prognosis
89
MDS: Recurrent Chromosomal Abnormalities
- monosomies 5 and 7
- deletions of 5q, 7q, and 20q
- trisomy 8
90
MDS: bone marrow: abnormal-appearing hematopoietic precursors
- megaloblastoid erythroid precursors
- ring sideroblasts(iron deposits in mitochondria of erythroid forms)
- granulocyte precursors with abnormal granules or nuclear mutations
- small megakaryocytes
91
MDS: Clinical Features: How Common?
- affects 15,000 pts per year
| - age between 50-70yr
92
MDS: Clinical Features: Symptoms
- as a result of cytopenias---> infections
- related to anemia
- hemorrhages
93
MDS: Clinical Features: Prognosis
- conventional chemo = poor
- transformation to AML = 10-40% of pts
- median survival time = 9-29mos
- worse in pts w/ increased marrow blasts, cytogenic abnormalities, or TP53 mutations
94
Common mutations in Myeloproliferative Disorders
- BCR-ABL
- mutated JAK2
- lead to constitutive activation of tyrosine kinases which mimic signals from normal growth factors
