269/270 - Leukemias (AML and ALL) Flashcards
On immunophenotyping, what markers prove that a cell population is made up of immature myeloid cells?
- Immature
- CD34+
- CD117+
- Myeloid
- CD13+
- CD33+
- MPO
Also - auer rods are important! Can’t see on flow but indicates myeloid lineage
Which translocation is most common in each of the following presentations of B-ALL?
- Infants:
- Children:
- Adults:
- Infants:
- t(v;11) - KMT2A/MLL
- The KMT2A part of chromosome 11 is moved somewhere else; not a specific location
- Children:
- t(12;21) - ETV6/RUNX1
- Adults:
- t(9;22) BCR-ABL1
- Can occur spontaneously or trasnform from CML
What are the diagnostic criteria for AML?
Bone marrow biopsy
- >20% blasts in bone marrow or blood
-
Evidence of myeloid differentiation
- Auer rods
- MPO+ (NSE+ = monoblasts)
- Myeloid-associated markers by immunophenotyping
What is the lineage-defining marker of T-cells?
CD3
What translocation is associated with acute promyelocytic leukemia?
What product is created?
t(15;17)
Creates PML-RARA; causes cells to arrest in promyelocytic stage
What is the lineage-defining marker of B-cells?
CD19
CD20 is acquired later; can be lost in malignancy (ex: classic nodular sclerosing hodgkin lymphoma)
Bone pain and refusal to bear weight are common symptoms of which hematopologic malignancy?
ALL
Due to intramedullary expansion of leukemic blasts
List the key differences in presentation between B-ALL and
T-ALL (often LBL)
- B-ALL
- Abrupt onset
- Bone marrow failure (thrombocytopenia, neutropenia, anemia)
- B symtoms (fever, night sweats, generalized lymphadenopathy)
- Bone pain (B for Bone Pain)
- T-ALL (LBL)
- High white count
- SVC syndrome (T for Tall like Superior Vena Cava)
- CNS involvement (T for Tall like Spinal Cord)
What is the most important prognostic factor in AML?
Chromosomal abnormalities
What is the cell of origin in AML?
Common myeloid progenitor
Which malignancy, in which population, is associated with t(12;21)?
Is this translocation prognostic?
B-ALL in children 1-10 years old
Favorable prognosis
What is the most common cancer of children?
ALL
Peak incidence of B-ALL is 3 years
What is the most important prognostic factor in ALL?
Time to response to induction chemotherapy
Fast response = good prognosis
Genomic alterations in AML can be used:
- For further classification
- For Prognostication
- For Targeted therapy
- For the detection of minimal residual disease
- All of the above
e. All of the above
Which part of which chromosome is most commonly involved in B-ALL in infants <1 year old?
11q23.3
Results in abnormal expression KMT2A
Can be translocated to various different locations (I think)
In the learning guide, the explanation for guiding question 2 is “B-ALL with t(v;11q23.3), KMT21 (or MLL) rearrangement is the most common leukemia in infants <1 year)”
In AML, the presence of which genetic mutation is associated with good prognosis?
NPM1 [AML, No Problem Mate]
(Also CEBPA, but less common)
FTL3-ITD = poor prognosis [AML, Fuck This Life]
Are abnromal karyotypes more useful for prognosis in B-ALL or T-ALL?
B-ALL
- t(v;11q23) - KMT2A/MLL = poor prognosis (infants <1)
- t(12;21) - ETV6-RUNX1 = good prognosis (children 1-10)
- t(9;22) - BCR-ABL = poor prognosis (adults)
Chromosome abnormalities are common in T-ALL, but not prognostic. Usually involves 14q, 7p
What is the “classic presentation” of acute promyelocytic leukemia (APL)?
DIC + Hemorrhage (ex: subarachnoid hemorrhage)
t(15;17) forms PML-RARA -> arrest in promyelocytic stage
What genetic syndrome is a risk factor for ALL?
Down syndrome
Which chemotherapy agents pose the greatest risk for developing AML?
-
Alkylating agents (cyclophosphamide, bendamustine)
- Usually has intermediate MDS phase
-
Topoisomerase-II inhibitors (Etoposide, anthracyclines)
- No intermediate phase; usually goes straight to AML
What is the most curable AML?
Acute promyelocytic leukemia (APL)
t(15;17) creates PML-RARA; treat with all-trans retinoic acid and arsenic trioxide
Which age group at presentation has the most favorable prognosis for ALL?
2-10 years old
What is the most common cell of origin in ALL (acute lympoblastic leukemia) or LBL (lymphoblastic lymphoma)
- ALL
- 85% is from B-cells (B-ALL)
- Very young children
- 85% is from B-cells (B-ALL)
- LBL
- 90% is from T-cells
- Adolescents
- 90% is from T-cells
What are the B-cell markers of immaturity? (2)
CD34
TdT
Immature T cells will have CD1a and CD3
Which malignancy, in which population, is associated with t(v;11q23)?
Is this translocation prognostic?
B-ALL in infants <1
often t(4;11)
Poor prognosis :(
Often predicts CNS involvement
In AML, the presence of which genetic mutation is associated with poor prognosis?
FTL3-ITD [AML, Fuck this Life]
NPM1 is associated with a good prognosis [AML, No Problem Mate]
What is the treatment for APL?
All-trans retinoic acid + Arsenic trioxide
Which populationis most commonly affeted by T-ALL/LBL?
What are the characteristic markers? (3)
Males, adolescents
Presents with mediastinal mass
TdT, cytoplasmic CD3, CD1a
What does CNS or testicular involvement predict for the prognosis of ALL?
poor prognosis :(
B-ALL with t(9;22) is most common in which population?
Is this translocation prognostic?
Adults
Poor prognosis
Can be a transformation from CML or arise spontaneously
What targeted treatments can be used in B-ALL?
Imatinib if t(9;22) translocation
Blinatumomab otherwise (Brings T-cells close to ALL cells)
What two translocations are associated with AML?
- t(8;21)
- inv(16)
- Atypical eosinophilic precursors
- Both have good prognosis, unless concurrent KIT mutation*
- Vs. mutations: NPM1 is diagnostic, FTL3 is prognostic (poor)*
