Acute leukemias Flashcards
What is an acute leukemia?
A clonal, neoplastic proliferation of hematopoietic cells, usually immature, presenting as a rapidly progressive disease.
What are the two categories of acute leukemias?
There are two basic categories of acute leukemia:
AML – Acute myeloid leukemia – leukemic cells resemble cells of one or more myeloid lineages
ALL – Acute lymphoblastic leukemia – leukemic cells resemble precursor (immature) lymphocytes
What is the etiology of acute leukemias?
how can you detect chromosomal abnormalities in leukemias?
How do you detect molecular abnormalities?
What are some abnormalities required to generate acute leukemias?
-The majority of acute leukemias have chromosomal abnormalities, detectable by cytogenetic tests (*karyotyping, FISH)
–>The large majority of acute leukemias also have molecular abnormalities (mutations, ITDs, etc.), detectable by molecular tests (PCR, NGS)
–>Usually, abnormalities required to generate an acute leukemia include:
- Block in ability to differentiate
- Increased autonomy of growth-signaling pathways
What are the risk factors for acute leukemia?
Previous_______ is the most common risk factor when one is present, specially if DNA alkylating agents and topoisomerase-II inhibitors were used.
- Majority of acute leukemias occur in the absence of a known risk factor.
- By far the most common risk factor, when one is present, is previous chemotherapy, especially
–>DNA alkylating agents and topoisomerase-II inhibitors
–>Previous exposure of active marrow to ionizing radiation
–Tobacco smoke
–**Benzene exposure
-Genetic syndromes, including Down syndrome, Bloom syndrome, Fanconi anemia, and ataxia-telangiectasia
ACUTE LEUKEMIAS –
Clinical Presentation
-Presenting signs/symptoms usually result from replacement of the normal marrow cells by leukemic cells. They might include:
Signs/symptoms of anemia:
- fatigue, malaise, pallor, dyspnea
Signs/symptoms of thrombocytopenia:
- bruising, petechiae, hemorrhage
Signs/symptoms of neutropenia:
fever, infections
What are some sign/symptoms derived directly from leukemic cells?
Why do thrombotic events occur? What is this known as?
- More rarely, presenting signs/symptoms may be directly attributable to effects of the leukemic cells. These include:
- Thrombotic events due to increased blood viscosity (known as **leukostasis**; seen in the setting of leukemia with very high WBC count).
- Disseminated intravascular coagulation (DIC), which can be initiated by the leukemic cells in some types of AML
- Direct infiltration of skin, gums, lymph nodes, and/or other tissues by leukemic cells.
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) –
Epidemiology
What are the two types of ALL?
75% of ALL occur in what population?
ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) –
Diagnosis
In patients what cells represent the majority of marrow cells?
Is there a % of cells to diagnose ALL?
Peripheral WBC count can be:
Markers:
GENERIC MARKERS OF IMMATURITY (also on myeloblasts) are________.
Common lymphoblast marker (not on mature lymphocyte)_____.
The markers of B cell lineage are____ and _____.
The markers on T cell lineage are______ and _____.
B-Lymphoblastic Leukemia
(B-ALL)
B-lymphoblasts usually lack markers of mature B cells such as______ and ________.
B-ALL is the typical ALL of___________.
–>B-ALL accounts for 80-85% of all cases of ALL
–>Besides expressing B cell-lineage antigens, B-lymphoblasts usually lack markers of mature B cells, such as CD20 and surface immunoglobulin.
–B-ALL is the typical ALL of childhood***
B-ALL Cytogenetic findings
B-ALL with t(9;22); BCR-ABL1
Has the so called ________ chromosome.
B-ALL with translocations of 11q23; MLL
B-ALL with t(12;21); ETV6-RUNX1
T-LYMPHOBLASTIC LEUKEMIA
(T-ALL)
It is more frequent in what populations?
Often presents as a ______ mass due to T-lymphoblastic lymphoma.
In contrast to B-ALL, T-ALL often has a high ______ count.
More common in ______.
ALL
What is the prognosis in kids?
in adults?
Prognostic values in ALL in general
Acute Myeloid Leikemia (AML)
It is mostly a disease of ______, with an average age of diagnosis at___.
- AML is a much more heterogeneous disease than ALL (many more types)
- AML is typically a disease of adults:
- Average age at diagnosis of AML: 65
- only ~10% of childhood leukemias are AML
- AML incidence is around 3 cases per 100K persons per year (similar to ALL)
Acute Myeloid Leukemia
The generic markers of immaturity (also present in lymphoblasts) are _________.
Common myeloid markers not present in lymphoblasts are:_____ and ______.
What feature allows the identification of myeloblasts?
-In addition, the presence of certain recurrent cytogenetic abnormalities (usually translocations) allows a diagnosis of AML to be made regardless of the blast count.
AML with t(8;21); RUNX1-RUNX1T1
Patients are usually _______.
Associated with AML with maturation.
Some mature ______ are still being produced.
What is the prognosis?
AML with inv(16) or t(16;16); CBFB-MYH11
Patients are _____.
Associated with what precursors?
Typically have _______ leukemia.
What is the prognosis like?
AML with t(15;17); PML-RARA
AKA Acute ________Leukemia.
Cells have ________ morphology.
APL
Why is it important to recognize?
How can you treat APL patients?
APL is associated with what disease?
APL is important to recognize quickly for 2 reasons:
1) The RARA gene encodes the retinoic acid receptor alpha protein. Signalling through this receptor is required for differentiation past the promyelocyte stage.
In APL, the PML-RARA fusion protein functions poorly as a retinoic acid receptor. However, adequate levels of signaling activity can be obtained with supra-physiologic doses of all-trans retinoic acid (ATRA)
Thus, APL patients do not required traditional induction chemotherapy used for other acute leukemias, which has significant rates of morbidity and mortality. APL patients can be treated instead with ATRA and arsenic salts, which have very little morbidity and almost no mortality.
2) APL is often associated with disseminated intravascular coagulation (DIC), a condition of widespread ongoing concurrent clot formation and clot lysis, which can be a medical emergency. Thus, identification of the acute leukemia as APL alerts the clinician to the possibility of DIC, and appropriate measures can be taken if necessary.
Cytogenetic abnormalities
Which one is common in Down syndrome patients?
Therapy-Related AML (T-AML)
AML, Not otherwise specified
- AML, NOS includes cases of AML lacking recurrent cytogenetic findings, and not known to be due to previous therapy
- AML, NOS may be subclassified based on the line of differentiation of the leukemic cells, as defined by morphology and immunophenotyping.
AML prognosis
