Acute Leukemias Flashcards
The gene fusion in APL fuses the ______ to another, so differentiation is blocked.
retinoic acid receptor-alpha (RARA) gene
What is an Auer rod?
small, stick-like structures in the cytoplasm
What is the treatment for APL?
retinoic acid and arsenic salts
In megakaryoblastic differentiation AML, the leukemic cells may express megakaryocytic antigens ____ and ____.
CD41, CD61
AML with t(1;22) RBM15-MKL1 shows _____ and is most often seen in _____.
megakaryoblastic differentiation; infants with Down Syndrome
B-ALL with abnormalities of _____ is frequently seen in neonates and young infants.
11q23 MLL
In AML with inv(16) or t(16;16) CBFB-MYH11, there is usually a mixture of increased ____ and _____.
myeloblasts; monocytes
Chromosomal abnormalities are found in 95% of ____ and 90% of ______.
AML patients; ALL patients
______ are found in 95% of AML patients and 90% of ALL patients.
Chromosomal abnormalities
What does CEBPA indicate?
positive AML,NOS
T-ALL frequently presents with lymphoblastic lymphoma, often manifesting as a ____.
large mediastinal mass
What is therapy related AML (t-AML)?
AML arising 2a to DNA damage from a prior therapy, like DNA alkylating agents, topo-II inhibitors, or ionizing radiation
Chemotherapy, especially with _____ and ____, is a risk factor for acute leukemia.
DNA alkylating agents; topoisomerase-II inhibitors
____ more frequently occurs in adolescents and young adults.
T-ALL
What are the 5 AML chromosome translocations?
- t(8;21) RUNX1-RUNX1T1 2. inv(16) or t(16;16) CBFB-MYH11 3. t(15;17) PML-RARA APL 4. t(1;22) RBM15-MKL1 5. 11q23 MLL
What is Fanconi Anemia?
inherited aplastic anemia; auto recessive or x-linked;
What is the incidence of AML?
3/100,000
t-AML 2a to topoisomerase-II inhibitors usually has a latency period of ____ and has a karyotype showing _____.
1-2 years; rearrangement of the MLL gene
T-ALL frequently presents with _____, often manifesting as a large mediastinal mass.
lymphoblastic lymphoma
In adults, ALL has a remission rate of ____ and cure rates of _____.
60-80%; less than 50%
What is the prognosis in t(1;22) RBM15-MKL1? Treatment?
relatively good; intensive chemo
___% of all cases of ALL occur in children under 6yo.
75
Some cases of APL give rise to ____, which the clinician should always be watching for.
DIC
What is the average age of AML diagnosis?
65yo
What are the signs of acute anemia?
anemia, pallor, thrombocytopenia, hemorrhage, ecchymoses, petechiae, fever, infection, adenopathy, hepatosplenomegaly, medistinal mass
75% of all cases of ALL occur in _____.
children under 6yo
B-ALL with _____ accounts for 25% of childhood cases and have a very favorable prognosis.
t(12;21) ETV-6RUNX1
In _____, the leukemic cells can express monocytic antigens CD64 and CD14.
monocytic differentiation AML
Acute leukemia is ____.
a clonal, neoplastic proliferation of immature myeloid or lymphoid cells
In ____, the leukemic cells may express megakaryocytic antigens CD41 and CD61.
megakaryoblastic differentiation AML
T-ALL accounts for ____% of ALL cases.
25-30
What does CBFB do?
encodes the beta subunit of core binding factor (CBF)
ALL has a good prognosis in _____; the complete remission rate is 95% and cure rates are about 80%.
children
AML with 11q23 MLL shows some degree of _____ and has a ____ prognosis.
monocytic differentiation; poor
What are the diagnostic criteria for AML?
increased myeloblasts accounting for >20% of nucleated cells
What are the symptoms of acute anemia?
fatigue, malaise, dyspnea, bruising, weight loss, bone or ab pain, neuro symptoms
Which gene encodes for the alpha unit of core binding factor (CBF), a transcription factor needed for hematopoiesis?
RUNX1
What are the 2 major categories of acute leukemia?
- acute myeloid leukemia (AML) 2. acute lymphoblastic leukemia (ALL)
___ frequently presents with lymphoblastic lymphoma, often manifesting as a large mediastinal mass.
T-ALL
How are ALL and AML differentiated?
flow cytometry, immunohistochemistry, and/or morphology
ALL has a _____ in children; the complete remission rate is 95% and cure rates are about 80%.
good prognosis
T-ALL more frequently occurs in _____.
adolescents and young adults
Name 5 poor prognostic factors in ALL.
- age 10 2. elevated WBC 3. slow response to therapy or residual disease after treatment 4. hypodiploidy (
Name the 3 translocations to know in B-ALL.
- t(9;22) BCR-ABL1 2. 11q23 MLL 3. t(12;21) ETV6-RUNX1
AML with t(8;21) RUNX1-RUNX1T1 is found in about ____% of all cases and usually is seen in _____. It usually has a ____ prognosis.
5; younger; relatively good
What is Ph+ ALL?
the t(9;22) Philadelphia chromosome; 25% of adult B-ALL cases
____ with abnormalities of 11q23 MLL is frequently seen in neonates and young infants.
B-ALL
How can you ID a myeloblast in the microscope?
Auer rods
Acute leukemia is _____ without treatment.
fatal
B-ALL with t(12;21) ETV-6RUNX1 accounts for ___% of childhood cases and have a very favorable prognosis.
25
AML with inv(16) or t(16;16) CBFB-MYH11 is found in about ____% of all cases and usually is seen in _____. It usually has a ____ prognosis.
5-10; younger; relatively good
B-ALL accounts for ____% of all cases of ALL.
80-85
The presence of ____ are the most important prognostic finding for AML,NOS.
molecular findings
B-ALL with t(12;21) ETV-6RUNX1 accounts for 25% of childhood cases and have a ____ prognosis.
very favorable
How are chromosomal abnormalities detected?
cytogenetic analysis (karyotypic and FISH), molecular analysis (RT-PCR)
How is ALL diagnosed?
no set % of lymphoblasts req- WBC can be increased, decreased, or normal. Lymphoblasts have CD34 and TdT
_______ is a clonal, neoplastic proliferation of immature myeloid or lymphoid cells.
Acute leukemia
What is Bloom Syndrome?
auto. recessive disorder predisposing to cancer early in life; small stature, facial anomalies, immunodeficiency
APL with t(15;17) PML-RARA has increased _____ instead of blasts.
abnormal promyelocytes
What is Ataxia Telangiectasia?
neurogenerative disorder; abnormal eye movements, immune deficiency due to a defective chromosome 11
The leukemic cells themselves can cause _____ or _____ problems.
hyperviscosity; thrombotic problems
B-ALL with abnormalities of 11q23 MLL has a ____ prognosis.
poor
B-lymphoblasts express ____, ____, and/or ____.
CD19, CD22, CD79a
What has the worst prognosis of all ALLs?
Ph+ ALL
What is a solid mass malignancy of precursor lymphoid cells called?
lymphoblasic lymphoma (LBL)
In adults, ____ has a remission rate of 60-80% and cure rates of less than 50%.
ALL
AML with inv(16) or t(16;16) CBFB-MYH11 is notable bc of the presence of ____ with _____, called _____.
immature eosinophils; abnormal basophilic granules; baso esos
Why does the t(8;21) cause problems?
RUNX1 and CBF genes are blocked, so blood cells can’t differentiate
APL accounts for ____% of AML, and is diagnosed when _____ is found.
5-10; t(15;17)
What does FLT3 ITD indicate?
negative AML,NOS
T-ALL occurs more commonly in ____ and ____.
males; adolescents and young adults
What is the incidence of ALL?
1-5:100,000
What antigens are only seen on immature T-cells?
CD99; CD1a
T-lymphoblasts express ____, ____, ____, ____, ____, ____, and/or _____.
CD2, CD3, CD7, CD4, CD8, CD99, CD1a
About 50% of all AML cases have a normal karyotype and are called ____.
AML-NOS (not otherwise specified)
ALL is divided into ____ and _____.
B-lymphoblastic ALL (B-ALL); T-lymphoblastic ALL (T-ALL)
The gene fusion in APL fuses the retinoic acid receptor-alpha (RARA) gene to another, so _____ is blocked.
differentiation
What do the cells look like in APL?
promyelocytes; hypergranular; Auer rods
What causes the s/s of acute leukemia?
loss of normal hematopoietic elements and blood cells
T-ALL more frequently occurs in ____.
adolescents and young adults
What is RUNX1?
a gene encoding for the alpha unit of core binding factor (CBF), a transcription factor needed for hematopoiesis
B-ALL with abnormalities of 11q23 MLL is frequently seen in _____.
neonates and young infants
Name 5 risk factors for acute leukemia.
- chemo (esp of DNA alkylating agents or topo inhibitors) 2. tobacco smoke 3. ionizing radiation 4. benzene exposure 5. genetic syndromes (Down, Bloom, Fanconi anemia, AT)
What do Auer rods indicate?
that the cell is a myeloblast
In ____, ALL has a remission rate of 60-80% and cure rates of less than 50%.
adults
___ has a good prognosis in children; the complete remission rate is 95% and cure rates are about 80%.
ALL
In monocytic differentiation AML, the leukemic cells can express monocytic antigens ____ and ____.
CD64, CD14
____accounts for 10-20% of AML cases and has a very poor prognosis.
t-AML
What unique antigens does a myeloblast express?
CD34, CD117 (C-kit), myeloperoxidase, CD33, CD13
t-AML 2a to alkylating agents or radation usually have a latency period of ___ and has a karyotype showing ____.
2-8 years; whole or partial loss of chromosome 5 and/or 7
____, _____, _____, and ______ are genetic syndromes that are risk factors for acute leukemia.
Down syndrome, Bloom syndrome, Fanconi anemia, ataxia telangiectasia
The gene fusion in ____ fuses the retinoic acid receptor-alpha (RARA) gene to another, so differentiation is blocked.
APL
What does NPM1 indicate?
positive AML, NOS
