Lec 13 Intro to WBC Flashcards
What are the origin myeloid malignancies?
involve cells of myeloid lineage [granulocytes, monocytes/ macrophages, erythrocytes, megakaryocytes/ platelets]
What is an acute leukemia?
leukemia with rapid onset; rapidly progressive and fatal
cells are not well differentiated or mature
What is a chronic leukemia?
leukemia with insidious onset
cells are mature and well differentiated
In leukemia are the malignant cells in the bone marrow or peripheral blood?
both!
What does it mean to have extramedullary disease?
leukemic cells infiltrate CNS, skin, liver, splee, lymph nodes
What characterizes acute leukemias?
clonal [from single transformed cell], characterized by impaired differentiation of hematopoietic cells; failure of apoptosis
have leukemic stem cells with self renewal capacity
What mech causes resistance to chemotherapy + relapse in leukemia?
evolution of sub-clones with additional mutations
What are some signs of acute leukemia?
anemia, hemorrhage, infection b/c the normal hematopoietic cells are crowded out by the accumulation of immature poorly functioning leukemic cells
What is acute myelogenous leukemia?
acute leukemia from myeloid lineage
What is median age of AML?
70 years old
What is acute lymphocytic leukemia [ALL]?
leukemia characterized by lymphoid lineage markers
Who gets ALL?
can be seen in chidlhood but can occur at any age
What are risk factors for acute leukemia?
- benzene exposure
- ionizing radiation
- prior exposure to chemo
What are some inherited risks for acute leukemia?
- down’s syndrome
- fanconi anemia
- bloom’s syndrome
What types of mutations associated with acute leukemias?
- structural chromosomal abnormalities [deletions, translocations], somatic mutations
How many subtypes of AML and ALL are there?
8 types of AML
3 types of ALL
What is a leukemia vs lymphoma?
leukemia = malignant cells in blood and marrow and can invade other organs
lymphoma = malignant cells confined to nodes/spleen; can sometimes invade blood and marrow and other organs
What are some underlying causes that can lead to secondary acute myelogenous leukemia?
- aplastic anemia
- paroxysmal nocturnal hemoglobinuria
- myelodysplasia
What is definition of acute leukemia?
> 30% blasts in blood or bone marrow
What is the strongest predictor of response to induction and survival?
cytogenetics
M2 AML is associated wtih what chromosomal translocation? What kind of prognosis?
(8;21) pretty good prognosis
What do you see on labs in acute leukemia?
- 50% normal or low WBC
- neutropenia
- hyperleukocytosis
- thrombocytopenia
- anemia
What chromosomal abnormality in M3 type of AML?
chromosome translocation (15;17)
What do you see on smear in M3 AML?
auer rods = cytoplasmic inclusions
lots of circulating myeloblasts
What is a possible complication of M3 AML?
development of DIC
How do you treat M3 AML?
all-trans retinoic acid [vit A] –> induces differentiation of myeloblasts
What type of chromosomal rearrangement in M4 AML?
inversion of chromosome 16
What do you see clinically in the M4 and M5 AML subtypes?
high white cells counts; extramedullary invovlement –> gingival hypertrophy + CNS involvement
What are some complications of acute leukemia?
- infection secondary to neutropenia –> candida, cellulitis, herpes zoster
- bleeding –> thrombocytopenia and DIC
What types of chromosome abnormalities in M3 AML?
abnormalities in chromosomes 5q and 7q
What subtype of ALL often seen in childhood ALL?
L1
What is the burkitt type of ALL?
L3
What happens in hyperleukocytosis in acute leukemia?
leukemic blast cells counts > 50,000 –> get leukostasis = the blast cells obstruct small blood vessels in CNS and lungs
–> intracranial hemorrhage, hypoxemia, headaches
What types of leukemia most likely to see organ infiltration?
ALL and M4/M5 subtypes of AML
What lab findings in leukemia?
high urinc acid level b/c of increased cell turnover
What do you see in bone marrow aspirate in acute leukemia?
hypercellular
normal hematopoietic cells replaced by monotonous population of immature cells; megakaryocytes decreased in number
may get dry tap b/c marrow so packed/sticky
What morphologic features distinguish myeloid from lymphoid leukemia?
presence of auer rod in myeloid leukemia; no auer rod in ALL
What does positive myeloperoxidase stain tell you?
tells you AML
What does positive sudan black stain tell you?
tells you AML
What does positive PAS stain tell you?
positive in ALL and erythroid leukemia AML- M6
What do you see in pre-B cell ALL?
- arise from early lymphoid progenitor
- express CALLA antigen [CD10]
- express cytoplasmic Ig
- TdT [terminal deoxynucleotidyl transferase]
What is prognosis fo CALLA type ALL?
good prognosis, seen in kids
What do you see in B cell ALL?
- known as burkitt’s type
- L3 morphology
- positive surface Ig expression
- chromosome translocation (8;14)
- TdT negative
What do you see in T cell ALL?
- T cell markers
- positive TdT stain
- chromosomal translocation (11; 14)
- identical to lymphoblastic lymphoma
What types of ALL have TdT [terminal deoxynucleotidy transferase]?
CALLA positive ALL
T cell ALL
T cell lymphoblastic lymphoma
t(9;22) is associated with what disorder? what is the gene involved?
CML
this is philadelphia chromosome = get bcr-abl hybrid
t(8;14) is associated with what disorder? what is the gene involved?
Burkitt lymphoma
get c-myc activation
t(11;14) is associated with what disorder? what is the gene involved?
mantle cell lymphoma
get cyclin D1 activation
t(14;18) is associated with what disorder? what is the gene involved?
follicular lymphoma
get bcl-2 activation
t(15;17) is associated with what disorder? what is the gene involved?
M3 type of AML
get destruction of retinoic acid gene; responds to all-trans retinoic acid
How can FISH and PCR be used in leukemia?
- to detect presence of a specific abnormality
- to follow response to therapy
- to detect evidence of recurrence
What are myelodyplastic syndromes?
clonal stem cell disease with hypercellular marrow and trilineage dysplasia; at risk for evolution to acute leukemia
What is treatment for myelodysplasia?
allogenic stem cell transplantation
What are pelger huet cells? what do they suggest?
they are hyposegmented neutrophils
suggest myelodysplastic syndrome
What is significance of Fms-like tyrosine kinase 3 [FLT3]?
mutated in 1/3 of patients with normal cytogenics AML; associated wtih increased risk of relapse and poorer survival
What is significance of wilm’s tumor [WT1] gene?
mutated in some pts with normal cytogenetics AML; associated with poorer prognosis
What is significance of nucleophosmin [NPM1] gene?
mutated in 50% of pts with normal cytogenetics AML; associated with higher WBC count, higher remission rates, reduced relapse risk
What is significance of CEBPa gene?
mutation see in normal cytogenetics AML; associated with better prognosis
What is significance of C-kit gene mutations?
see with pts with AML; have owrse prognosis
What is prognosis of majority of adult leukemia pts?
most relapse b/c not all leukemic stem cells are eradicated
What is purpose of induction therapy?
intended to achieve a complete remission
What is purpose of post remission therapy?
prevent relapse
What is standard induction chemo regimen for AML?
7+3
What are some complications of induction therapy?
N/V, diarrhea, skin damage, neuro tox, BM aplasia –> anemia, thrombocytopenia, neutropenia
What is tumor lysis syndrome?
when many leukemic cells lysed by chemo at same time –> metabolic waste products release –> hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and renal failure
What are some targeted treatments for AML M3 type [acute promyelocytic leukemia]?
- all-trans-retinoic acid [ATRA] –> induces differentiation/maturation of promyeloblasts
- arsenic trioxide [ATO] –> induces apoptosis
