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 and topoisomerase-II
What are the biggest risk factors for acute leukemia?
previous chemotherapy (especially DNA alkylating agents and topoisomerase-II) and 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?
CD34- a marker of immaturity also expressed in myeloblasts
TdT- a nuclear enzyme that is specific to lymphoblasts (not expressed in myeloblasts or mature lymphocytes).
In B-ALL, the leukemic lymphocytes express B cell markers. Which important markers should they contain and which should they lack?
positive- CD19, CD22, and/or CD79a (B-cell lineage antigens)
negative- CD20 and surface immunoglobulin (markers of mature B cells)
What cytogenetic findings can occur with B-ALL?
-t(9;22) BCR-ABL1
Not all cases of B-ALL contain the translocation but the ones that do result in the philadelphia chromosome. So we say that the patient is Ph + B-ALL.
-t(12;21) ETV6-RUNX1
-B-ALL with translocations at the MLL gene
How is the t(9;22) BCR-ABL1 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?
t(12;21) ETV6-RUNX1 (the others have a poor prognosis with t(9;22) being the worst).
Why might we find a large mediastinal mass associated with T-ALL?
T-ALL often presents with a component of T-LBL. In TLBL the T cells hang out in the thymus and a mass develops there (in the mediastinum).
T-ALL/T-LBL favors what gender?
affects males over females
What markers are seen in cells with T-ALL?
CD2, CD3, and/or CD7 (these are typical T-lineage antigens)
CD4 and/or CD8 (these tell what kind of T cell the t cell is (helper vs CTL) and both can be expressed concurrently)
CD99 and CD1a (these are antigens only seen in immature T cell and sometimes expressed by T-ALL cells)
ALL has the worst prognosis for what age group?
Adults and adolescents (ALL kills Adults and Adolescents (A’s)). Even though affects mostly kids under 6.
AML affects which age group most?
adults. ALL affects kids, AML affects adults. L before M kids before adults
How do you diagnose AML?
there should be increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood. Exceptions to this rule only in the presence of specific cytogenetic findings.
An Auer Rod identifies a cell as what kind?
a myeloblast. An Auer rod is an azurophilic granule that forms a small stick-like structure in the cytoplasm… just for your information
What markers are typically seen in myeloblasts?
CD34- a generic marker of immaturity seen in myeloblasts and lymphoblasts
CD117 (also called C-kit), Myeloperoxidase- these are myeloid antigen markers
Also these cells should be negative for tDt
What does it mean if a myeloblast expresses CD64 or CD14?
This is indicative of monocytic differentiation where leukemic cells (AML) express antigens typical of monocytes instead of myeloblasts.
What does it mean if a myeloblast expresses CD41 or CD61
this is indicative of megakaryoblastic differentiation where leukemic cells (AML) express antigens typical of megakaryocytes instead of myeloblasts.
A high nucleus:cytoplasm ratio is typical of what kind of cell?
blasts
There are five kinds of AML, what are they?
t(8;21) RUNX1-RUNX1T1 inv(16) or t(16;16) CBFB-MYH11 t(15;17) PML-RARA t(1;22) RBM15-MKL1 abnormalities with MLL gene
how does t(8;21) RUNX1-RUNX1T1 AML work?
RUNX1 encodes alpha unit of core binding factor (CBF). This is a transcription factor needed in hematopoiesis. The fusion blocks transcription of CBF dependent genes and thus blocks 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.
usually see baso-eos and is termed a myelomonocytic leukemia
