18) Introduction to leukemias Flashcards
2 characteristics that distinguish benign from malignant tumors
metastasis
differentiation
benign neoplasm that will mutate into a malignant neoplasm
premalignant
types of malignant neoplasms in BM
- leukemia (BM and PB)
- aleukemia leukemia (BM, not PB)
- lymphoma (LN)
cell stages that mutations usually occur in
- committed progenitor (myeloid or lymphoid)
- pluripotential stem cell
inactivated/unaltered potential cancer-causing genes
proto-oncogenes
oncogenes result in…
unregulated cell proliferation without differentiation
body’s defense against oncogenes
function
potential problem
- tumor suppressor gene (TSG)—p53 gene
- suppresses cell proliferation and neoplastic transformation
- homozygous mutation results in tumor growth
over 50% of cancers have —— gene suppression
p53/TSG
evidence for theory that it takes multiple mutations to cause a cancer
patients with other mutations have a higher risk of developing acute leukemia
- Down syndrome
- MPD or MDS
- chronic leukemia
affect activation of oncogenes
- genetic susceptibility
- somatic mutation (radiation, benzene, drugs)
- viral infection (especially retroviruses)
- immunosuppression (hereditary, drugs)
3 general categories of heme neoplasms
- myeloproliferative disorders (MPD)
- myelodysplastic syndromes (MDS)
- acute leukemias
2 classifications of leukemias
- FAB (French American British) 1976
- WHO 2016
the FAB system is based on…
- blast morphology
- cytochemical stains
leukemic hiatus
we see many blasts and mature cells, but few in-between states
characteristic of acute leukemia
all AML arise from…
CFU-GEMM
2 different FAB ways to subtype ALL
L1
L2
L3
or
T-cell
B-cell
Null cell
categories of ALL based on morphology & heterogeneity of BM blasts
- L1: homogeneous
- L2: heterogeneous
- L3: Burkitt’s lymphoma (vacuolated lymphs)
M0 - M7 are subtypes of…
AML
neoplastic cell in MPD and MDS
pluripotential SC
subgroups of MPN
- CML (↑ grans)
- polycythemia vera (↑ rbcs)
- essential thrombocythemia (↑ plts)
- agnogenic myeloid metaplasia/myelofibrosis (↑ fibrotic marrow)
subgroups of MDS
- refractory anemias (RA, RARS, RAEB, RAEB-T)
- CMML (like CML + monos)
exception to characteristics of an MDS
CMML
↑ grans and monos in PB
WHO classification is based on…
- cell lineage
- morphology
- immunophenotyping
- genetic features
- clinical syndrome
6 major myeloid groups based on WHO criteria
- MPN
- MDS/MPN
- MDS
- AML
- Acute leukemia of ambiguous lineage
- Myeloid & lymphoid neoplasms with eos and rearrangement
5 major lymphoid groups based on WHO criteria
- Precursor lymphoid neoplasms (ALL)
- Mature B-cell neoplasms (CLL)
- Mature T-cell and NK neoplasms
- Hodgkin’s lymphoma
- Posttransplant lymphoproliferative disorders
peak leukemia incidence ages
2-5 years
> 50 years
4 types of leukemia typical age groups
ALL: 2-5 years
CLL: adults >50 years
AML: adults, some children
CML: adults, middle age to older
typical leukemia findings on presentation
- anemia
- thrombocytopenia
- neutropenia/recurring infections
- bone pain
- hepatosplenomegaly, lymphadenopathy (chronic)
examples of where heme neoplasms can infiltrate body
- skin (especially those involving monos)
- CNS (espeically ALL)
green tumor of immature WBCs resulting from MPO activity
chloroma
chloromas especially found in —— and ——
AML
CML
anemias related to heme neoplasms are usually ——-/——-
normo/normo
auer rods are found in ——— and ——– cells
most commonly in…
presence rules out…
blasts and pros
M1 and M2 AML
ALL
————– erythropoiesis may be present in BM during leukemia, and does not respond to…
megaloblastoid
B12/folate tx
chemical signs of rapid cell turnover in leukemia
↑ uric acid (product of nucleic acid metabolism)
↑ serum LDH (correlates with concentration of leukemic cells)
now a last resort diagnostic method
cytochemical stains
not used at all for chronic leukemias
number and type of surface markers can define… (3)
- lineage
- stage of development
- clonality
immunophenotyping is most useful in the dx of…
ALL
t(15;17)
acute promyelocytic leukemia
t(9;22)
CML (Philadelphia chromosome)
used to catch the 5% of CML patients without Philadelphia chromosome
molecular methods that detect BCR/ABL mutation
abnormal hormone receptor found in acute promyelocytic leukemia
retinoid acid receptor alpha (RARA)
molecular analysis is most helpful in dx of … (3)
- acute promyelocytic leukemia
- CML
- T & B cell ALLs
—— of children treated for ALL go into long-term remission
adults treated for ALL have a ——- year survival rate
> 90%
2 year
assess statistical data to develop protocols for leukemia tx
cooperative oncology groups
cancer and leukemia groups
definition of minimal residual disease
- absence of leukemic blasts in BM and PB
- negative cytogenetics
- positive molecular tests (PCR, FISH)
chemo drugs typically used and action
- antimetabolites (kill rapidly dividing cells)
- alkylating agents (kill resting & proliferating cells)
- antibiotics (interfere with cell replication)
3 phases of ALL tx
- induction (achieves remission)
- CNS prophylaxis
- maintenance chemo (2-3 years in children)
AML tx is the same as ALL, except…
no CNS prophylaxis
permanent remission is rare and treatment is conservative
CLL
few are cured, so tx is supportive
MPN and MDS
BM transplant most successful in patients…
< 40 years
treatment before BM transplant
chemo & irradiation until remission is achieved
can be used if there is no well-matched BM donor found
autologous donation
autologous donations must be collected when……
and treated with…
patient in remission
mAb to remove leukemic cells
cyropreserved
—— days after a SC transplant, new cells begin to be produced
10-21
synthetic GFs that can be used in tx
- EPO
- G-CSF
- GM-CSF
- IL-11 (megakaryos)
chemo as a procoagulant can precipitate ——–, especially in patients with…
DIC
acute promyelocytic leukemia (pro granules are potent coag cascade activators)
standard complication of chemo that must be monitored
pancytopenia—infection, anemia, bleeding
supportive therapy used in addition to chemo
- transfusions
- antimicrobials
