Flashcards in Acute Leukemia Deck (62):
What is acute leukemia?
Clonal, neoplastic proliferation of immature myeloid or lymphoid cells.
What are the two major categories of acute leukemia?
1. Acute myeloid leukemia (AML)
2. Acute lymphoblastic leukemia (ALL)
What is the cause for the signs and symptoms of acute leukemia?
The loss of normal hematopoietic elements, and subsequently a loss of normal peripheral blood cells
True or False:
Acute leukemia is rapidly fatal without treatment
What is the most common etiology of acute leukemia?
What are two consequences of chromosomal abnormalities in acute leukemias?
1. Maturation/ differentiation is blocked
2. Cells are not dependent on external factors for growth stimulation
Acute myeloid leukemia includes which types of cells?
Acute lymphoid leukemia includes which types of cells?
B or T-cell lineages
Name some risk factors for acute leukemia.
Can acute lymphoblastic leukemia present as a solid mass?
Yes. It is called lymphoblastic lymphoma or LBL
What are the two main types of ALL?
1. B-lymphoblastic ALL (B-ALL)
2. T-lymphoblastic ALL (T-ALL)
What patient population does ALL most commonly present in?
Children under 6
What would you expect the peripheral white blood cell count to be in a patient with ALL?
It could be increased, normal, decreased
What cell surface marker can be found on the surface of lymphoblasts?
What enzymes do lymphoblasts express that can be used to identify them?
Hint: It is not expressed in mature lymphocytes & it adds nucleotides to V(D)J exons during antibody recombination
Terminal deoxynucleotidyl transferase (TdT)
Are the majority of ALL cases B-ALL or T-ALL?
What three B-lineage antigens are found on B-lymmphoblasts?
Do B-lymphoblasts express CD20?
What are three cytogenetic changes seen in B-ALL?
1. B-ALL with t(9;22)(q34;q11.2); BCR-ABL1
2. B-ALL with translocations of 11q23; MLL
3. B-ALL with t(12;21)(p13;q23); ETV6-RUNX1
What protein product is produced by t(9;22)?
This is called the Philadelphia Chromosome
BCR-ABL fusion protein 190kd
Only 25% of cases of adult B-ALL involve the Philadelphia chromosome. How does the presence of this protein effect the prognosis?
B-ALL with Philadelphia chromosome has the worst prognosis of all subtypes of ALL.
B-ALL with abnormalities of MLL is frequently seen in what patient population?
What is the prognosis?
Neonates and young infants
B-ALL with ETV6-RUNX1 is seen in what patient population?
25% cases of childhood B-ALL
Very favorable prognosis
What type of leukemia is more often seen in adolescents and young adults?
T-ALL more frequently presents with a component of lymphoblastic lymphoma (T-LBL). Where does this mass most often present?
It presents as a large mediastinal mass.
How does T-ALL present?
High white blood count
Does T-ALL/ T-LBL favor males or females?
What T-lineage antigens are expressed on T-lymphoblasts?
CD2, CD3, &/ or CD7
CD4 and CD8 CONCURRENTLY
CD99 and CD1a
What factors influence the prognosis of ALL?
AGE: worse in infants (10, and adults
WHITE BLOOD CELL COUNT: worse for markedly elevated WBC count
SLOW RESPONSE TO THERAPY/ SMALL AMOUNTS OF RESIDUAL DISEASE AFTER THERAPY
NUMBER OF CHROMOSOMES: very favorable prognosis for hyperdiploidy; poor prognosis for hypodiploidy
B VS. T LINEAGE: T-ALL seems to have a worse prognosis than B-ALL
What is the average age of diagnosis of AML?
65 years of age
How is AML diagnosed?
Increased myeloblasts accounting for 20% or more of nucleated cells in the marrow or peripheral blood
What are Auer rods?
Fused azurophilic granules forming small stick-like structures in the cytoplasm.
What cells do Auer rods differentiate.
Myeloblasts are generic looking. Aeur rods differentiate myeloblasts from lymphoblasts
What cells are Auer rods found?
Only abnormal myeloblasts
Myeloblasts often express what cellular markers?
CD34-A generic marker of immaturity
If monocytic differentiation occurs in AML what cellular markers can be seen?
If megakaryoblastic defferentiation occurs in AML what cellular markers can be seen?
What type of genetic abnormality is characteristic for AML?
How are balanced translocations detected?
Cytogenetic analysis (karyotyping or FISH)
Molecular analysis (RT-PCT)
What protein is produced in AML with t(8;21)(q22;q22); RUNX1-RUNX1T1?
RUNX1 encodes alpha unit of core binding factor (CBF), a transcription factor needed for hematopoiesis. The fusion protein blocks transcription of CBF-dependent genes, thus blocking differentiation.
What is the general prognosis of AML with t(8;21)(q22;q22); RUNX1-RUNX1T1?
Relatively good prognosis
What subtype of AML is characteristic of baso eos in the bone marrow?
AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11
What are "baso eos"?
Immature eosinophils with abnormal baasophilic granules in addition to their eosinophilic granules
What cells are often seen in AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11?
Increased myeloblasts and increasedmonocytes thus a "myelomonocytic leukemia"
Describe the protein produced in AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11?
CBFB encodes the beta subunit of core binding factor (CBF), a transcription factor needed for hematopoiesis. The fusion protein blocks transcription of CBF-dependent genes, thus blocking differentiation.
What is the general prognosis for AML with inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11?
Relatively good prognosis
Describe the cells in acute promyelocytic leukemia with t(15;17)(q22;q12); PML-RARA.
Abnormal promyelocytes predominate instead of blasts.
Hypergranular promyelocytes with many Auer rods (faggot cells)
How can acute promyelocytic leukemia be treated?
Supra-physiologic doses of all-transretinoic acid (ATRA) in combinatoinn with arsenic salts
APL can give rise to what life-threatening event?
Disseminated intravascular coagulation (DIC)
Describe the cells in AML with t(1/22)(p13;q13); RBM 15-MKL1.
Usually shows megakaryoblastic differentiation
What specific patient population is at risk of developing AML with t(1/22)(p13;q13); RBM 15-MKL1.?
Infants with Down syndrome
What is the general prognosis of an individual with AML with t(1/22)(p13;q13); RBM 15-MKL1.?
Relatively good prognosis with intensive chemotherapy
Describe the cells of AML with abnormalities of 11q23; MLL.
Frequently shows some degreee of monocytic differentiation
What is the general prognosis of AML with abnormalities of 11q23; MLL?
AML (t-AML) can be caused by what therapies?
t-AML secondary to alkylating agents or radiations occurs due to what cytological abnormality?
What is the latency period?
Whole or partial loss of chromosomes 5 and/or 7
t-AML secondary to topoisomerase-II inhibitors occurs due to what cytological abnormality?
Rearrangement of the MLL gene (11q23)
Generally all types of t-AML have what prognosis?
Monocytic differentiation is important to note as leukemic monocytes because...
They often infiltrate the skin and gums, resulting in many small lesions
Megakaryoblasts in AML, NOS (not otherwise specified) usually are accompanied by what life threatening disorder?
What is the most important prognostic finding for AML, NOS?
The presence of certain molecular findings
1. FLT3 ITD- NEGATIVE prognostic factor
2. NPM1- POSITIVE prognostic factor
3. CEBPA- POSITIVE prognostic factor