AML Flashcards
(25 cards)
What are the chromosomal abnormalities commonly associated with therapy related acute myeloid leukemia (AML)?
11q23 (MLL gene) or 21q22 (RUNX1)
These abnormalities can occur in therapy-related AML (t-AML) after exposure to certain drugs or environmental factors.
What environmental exposures are linked to the development of therapy-related AML (t-AML)?
- Benzene
- Ionizing radiation
These exposures can increase the risk of developing t-AML.
What is the increased risk associated with leukocytosis in AML patients?
Pulmonary and CNS complications due to microinfarction and hemorrhage from leukostasis
Patients with >50,000 leukemic blasts per uL are particularly at risk.
What molecular tests are important for risk stratification in AML?
- FLT3
- NPM1
- CEBPA
- ASXL1
- RUNX1
- TP53
- IDH1/IDH2
These tests help identify therapeutic targets and assess disease risk.
What defines acute myeloid leukemia (AML) in terms of blast percentage?
Greater than or equal to 20% myeloblasts, monoblasts, or promonocytes in peripheral blood or bone marrow
Certain cytogenetic abnormalities allow for classification as AML regardless of blast count.
What are some important immunophenotypic markers in AML?
- HLA-DR
- CD34
- CD117
- CD13
- CD33
These markers assist in the immunophenotypic characterization of AML.
What factors are considered adverse prognostic features in AML?
- Advanced age at diagnosis
- Extramedullary disease (including CNS leukemia)
- Disease related to previous chemotherapy or radiation treatment (t-AML)
- Presence of an antecedent hematologic disorder
Typically, myelodysplastic syndromes (MDS) or myeloproliferative disorders are antecedent conditions.
What is the genetic abnormality associated with AML with t(8;21)(q22;q22)?
RUNX1-RUNX1T1
This abnormality is one of the recurrent genetic abnormalities in AML.
What percentage of patients with newly diagnosed AML have acquired chromosomal abnormalities?
60%
These abnormalities are acquired and clonal.
What defines a complex karyotype in AML?
More than 3 abnormalities
Found in 10% to 20% of patients.
Which translocation is associated with excellent outcomes in APL?
t(15;17)(q22;q12-21)
This is a well-known favorable prognostic marker.
What is the most common cytogenetic subset of AML?
Patients with a normal karyotype
They generally fall into an intermediate-risk group.
What is the significance of NPM1 mutations in AML?
Heterozygous mutations in exon 12 are found in 40% to 60% of patients with a normal karyotype
Mutated NPM1, with wild-type FLT3 or low allelic ratio FLT3 ITD, is associated with a favorable prognosis.
What mutations are associated with favorable clinical outcomes in AML?
Biallelic mutations of CEBPA
CEBPA encodes a myeloid transcription factor important for normal granulopoiesis.
True or False: All AML patients with a normal karyotype have the same prognosis.
False
Intermediate-risk patients have variable outcomes due to molecular heterogeneity.
What are some genes that define epigenetic pathways in AML?
DNMT3A, IDH1, IDH2, TET2
Mutations in these genes have been described in many patients with AML.
Fill in the blank: The primary disease characteristics used in assigning prognosis for patients with newly diagnosed AML are _______.
chromosomal and molecular abnormalities
These abnormalities are critical in risk assessment.
Two types of t-AML
- Exposure to alkylating agents or RT
- Exposure to topoisomerase II inhibitors
t-AML c alkylating agents or RT setting?
- increase c age
- 5-10 yr latency
Often antecedent Tx-related myeloid neoplasms (MDS) - unbalanced loss of genetic material involve ch5 or ch7 and/or TP53 mutation
t-AML c topoisomerase II Inhibitors
Less common (20-30% of t-AML)
- 1-5 ye latency period
- Less often preceded by MDS
- Balanced recurrent chromosome translocations (11q23 MLL gene or 21q22 RUNX1)
Relapsed AML c FDA approval targeted agents
- Gilteritinib only (ADMIRAL)
- Ivosidenib
- Enasidenib
APL characters
Low expression or absence of HLA-DR, CD34, CD117, CD11b
Pediatric AML common translocations
KMT2A (25% childhood AML — 50% infant AML cases)
FDA approval drug for children with ND-AML CD33+ and also relapsed AML in children
Gemtuzumab ozogamicin
