Acute Leukemias Flashcards
What two things need to occur in order for an acute leukemia to develop such that it can outcompete the bone marrow?
- maturation/differentiation is blocked
2. cells are not dependent on external growth factors (increased autonomy of growth signaling pathways.
Define an acute leukemia.
a clonal, neoplastic proliferation of immature myeloid or lymphoid cells
What are the two chemotherapies that cause the biggest risk for developing acute leukemia?
- DNA alkylating agents
2. topoisomerase-II
What are the biggest risk factors for acute leukemia?
- previous chemotherapy (especially DNA alkylating agents and topoisomerase-II)
- ionizing radiation
What age group does ALL typically occur in?
Children
75% of cases occur in kids under 6 years old
Cell markers are important in the diagnosis of leukemias. What important markers do lymphoblasts have in ALL and what does each marker signify?
TdT- a nuclear enzyme that is specific to lymphoblasts (not expressed in myeloblasts or mature lymphocytes).
CD34- a marker of immaturity also expressed in myeloblasts
In B-ALL, the leukemic lymphocytes express B cell markers. Which important markers should they contain?
CD19 and CD22 but NOT CD20
What 3 cytogenetic findings can occur with B-ALL?
- t(9;22) aka Ph +
- translocation of 11q23
- t(12;21)
How is the t(9;22) translocation different in B-ALL than it is in CML?
There is a different breakpoint in the BCR gene:
-In B-ALL the result is a 190kd fusion protein.
-In CML it is a 210kd protein
(Think B before C, and 190 before 210).
Of the three cytogenetic possibilities associated with B-ALL which one has a very favorable prognosis? Worst prognosis?
t(12;21)-best
T (9;22)- worst
- think of 9;22 being worse than 911
- Think of B-ALL as affecting mostly BABIES
Why might we find a large mediastinal (thymic) mass associated with T-ALL?
T-ALL often presents with a component of T-LBL (lymphoblastic lymphoma). In TLBL the T cells hang out in the Thymus and a mass develops.
Most common in Teenagers. Remember T-ALL=Thymus + Teenagers
T-ALL/T-LBL favors what gender and age group?
Teenage Males
What markers are seen in cells with T-ALL?
-CD2, CD3, and/or CD7 (most important)
ALL has the worst prognosis for what age group?
Adults and adolescents, even though affects mostly kids under 6.
*ALL kills Adults and Adolescents (A’s).
AML affects which age group most?
Adults. ALL affects kids, AML affects adults.
*L before M kids before adults
How do you diagnose AML?
Neoplastic accumulation of myeloblasts (>20%) in bone marrow.
*Exceptions to this rule only in the presence of specific cytogenetic findings.
An Auer Rod identifies a cell as what kind?
Myeloblast.
An Auer rod is a crystal aggregates of MPO.
MPO is characteristic of Myeloblasts.
What markers are typically seen in myeloblasts?
Myeloperoxidase (MPO)- Most important
CD117 (also called C-kit)
A high nucleus to cytoplasm ratio is typical of what kind of cell?
Blasts
There are five kinds of AML, what are they?
- t(8;21) RUNX1 “alpha core binding factor”
- inv(16) or t(16;16) “baso eos” (beta core binding factor)
- (15;17) PML-RARA (APL) **most important
- t(1;22) associated with downs
- abnormalities with 11q23 of MLL gene
How does t(8;21) RUNX1-RUNX1T1 AML work?
RUNX1 encodes alpha unit of core binding factor (CBF), which is needed for differentiation.
How does AML with inv(16) or t(16;16) CBFB-MYH11 work? what are typical characteristics?
CBFB encodes the beta subunit of core binding factor (CBF).
Differentiation is prevented. See abnormal “baso-eos”
What is APL? how does it work?
- A subtype of AML (acute promyelocytic leukemia).
- Promyelocytes predominate instead of blasts because no RARA is produced.
- t(15;17)
- Typical morphology is FAGGOT CELLS! Many Auer rods.
How can you treat patients with APL?
High dose all trans ATRA. High doses overcomes the wonky RARA receptor.
NO CHEMO NECESSARY!
Some cases of APL can lead to what blood complication?
DIC- Disseminated intravascular coagulation
This is why it is important to know if an acute leukemia is APL. You can be aware of the DIC possibility
AML t(1;22) is seen in patients with ________ and often shows ______ differentiation.
Down syndrome
Megakaryoblastic
t(1;22) is also known as Acute Megakaryoblastic Leukemia
What is t-AML and how can you get it?
Therapy related AML.
Results from chemo like topoisomerase-II, alkylating agents, or ionizing radiation.
Problems in this tissue arise in patients with Acute Monocytic Leukemia.
What are the gums?
Which cell lineage expresses TdT?
Lymphoblasts
The broncos LBs scored TDs ALL day
LBs=Lymphoblasts
TDs=TdT marker
ALL= ALL- most prominent leukemia
What evidence exists for “leukemic stem cells”?
Tumor relapses after chemo resulted in homogenous CD34+/CD38- cells. Since heterogeneity is found in most cancer metastases, it reinforces that LSCs exist
Explain why patients with leukemia may exhibit fatigue, bruising, hemorrhage, and frequent infection.
Leukemias cause “crowding out” of other blood cells in the bone marrow.
Fatigue- Anemia due to dec. RBC
Bruising, hemorrhage- Thrmobocytopenia
Frequent infection- Neutropenia
What is the genetic marker of immaturity in Leukemia?
CD34
What are the 5 factors affecting prognosis of ALL?
What combination of these factors would give the BEST prognosis.
- Age - 1-10
- WBC count- Low WBC
- Response to therapy- Fast or normal response
- # of chromosomes- Hyperdiploidy (51-65)
- B vs T lineage - B-ALL
List 3 molecular markers currently used to predict prognosis in patients with AML with normal karyotype. Which one of these is the “trump” for prognosis?
FLT3- Poor prognosis
NPM-1 Good prognosis
CEBPA- GOod prognosis
Just remember FLT3, it is the trump and the only negative indicator
