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!
