UNIT 2.2 Flashcards by FRANCHESCA MAUREEN CUISON

One single mutation can already
be converted to

oncogene

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The effects shall be
seen on the ________ of the cancer cells.

proliferative advantage

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hindrance in differentiation.

maturation block

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Continuous division → defective apoptosis →
proliferation of many cells =

Continuous division → defective apoptosis →
proliferation of many cells = Leukemia.

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Once myeloblast, promyelocyte, and myelocyte
are seen in the peripheral blood, thereʼs an
indication of abnormality.

TRUE

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The initial mutation in leukemia involves a _____

hereditary cancer mutation or familial predisposition syndrome.

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increased expression

proto-oncogenes

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disrupted function = no
suppression or regulation of growth = uncontrolled cell
growth and accumulation of mature/immature leukocytes
in bone marrow or peripheral blood

tumor suppressor genes

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If there is no
infection, most likely
it is a ______ form
of leukemia.

chronic

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involves myeloblast / myeloid
progenitor cells (acute myelogenous leukemia) or
lymphoblasts / lymphoid progenitor cells (acute
lymphoblastic leukemia)

ACUTE LEUKEMIA

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proliferation of blasts overwhelms
the bone marrow → blast seen in peripheral blood → normal elements are replaced by leukemic blasts → suppression of erythropoiesis → resulting to anemia /
thrombocytopenia

chronic leukemia

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(a group of
metabolic complications caused by breakdown products
of dying cancer cells), leading to acute uric acid
nephropathy and renal failure, as well as hyperkalemia,
hyperphosphatemia, hyperuricemia, hypocalcemia.

tumor lysis syndrome

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● More sensitive
● Old standard

FAB

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● More strict
● Standard classification
of diagnosis

WHO

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More than >30% blasts suffice
for the diagnosis of acute
leukemia

FAB

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More than or equal to >20%
blasts suffice for the
diagnosis of acute leukemia

WHO

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Emphasizes molecular and
cytogenetic changes
Morphology, cytochemistry,
immunophenotype, genetics,
and clinical features

WHO

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Based primarily on morphology
and cytochemical staining of
blasts

FAB

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Enzyme found in the primary
granules of granulocytic cells
● Myeloperoxidase enzyme
deteriorates
○ Stain should be done
only in fresh specimens
anticoagulated with EDTA
or heparin.

MPO

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Sensitive test
○ Enzyme would diminish if
the blood is older
○ Old samples = false
negative results

MPO

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Non-enzymatic stain

SBB

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found in
leukemic blasts and
promyelocytes test
strongly MPO positive.

AUER RODS

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Used to differentiate acute
myeloid from acute
lymphocytic leukemia

MPO AND SBB

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(+) AML, (-) ALL
○ Lymphocytes do not
exhibit MPO activity
○ Lymphoblast in ALL are
MPO negative

MPO

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Peroxidase activity produces _______ in the cytoplasm of granulocytes.

dark brown/ black granules/precipitate

Peroxidase activity produces _______ in the cytoplasm of granulocytes.

dark brown/ black granules/precipitate

Stains Auer Rods (fusion of primary / azurophilic granules)

MPO

Stains fats / lipids present granulocytes and in monocytes

SBB

● (+) AML, (-) ALL ● Dark purple-black granules

SBB

Reaction only in the blast cell is used as the determining factor

MPO AND SBB

Marker for lipids and phospholipids ● Mature granulocytes can be stained (normal finding)

SBB

Marker for glycogen glycoproteins, mucoproteins, and high molecular weight carbohydrates

PAS

(-) AML, (+) ALL, (+) Erythroblast

PAS

L1 (+), L2 (+), L3 (-)

PAS

(+) FAB M6 Erythroleukemia / Di Guglielmo syndrome

PAS

Not used to differentiate ALL from the rest of leukemia, but to detect only one specific type: hairy cell leukemia

ACP

Tartrate Resistant Acid Phosphatase (+) (+) ALL

acid phosphatase

Only ______ from hairy cell leukemia are resistant to inhibition with tartrate and continue to stain positive.

hairy cells

abnormal B lymphocytes, with cytoplasmic appearance, classified under chronic lymphoid neoplasm ○ TRAP (+)

HAIRY CELLS

Another cell TRAP (+) → _____ ○ Cutaneous T cell lymphoma, present in cases of mycoses fungoides ○ Spread in blood and became systemic

sezay cells Sezay Syndrome)

Also called Neutrophil Alkaline Phosphatase ● Uses fresh specimens anticoagulated with heparin.

LAP

Detects alkaline phosphatase enzyme activity. ● Used to differentiate CML from neutrophilic leukemoid reaction. ● Used to detect enzyme activity in primary granules of neutrophils

LAP

100 neutrophils are graded 0 to 4+ based on stain intensity. ○ Ask two microscopist to count and get the average score; ○ Depends on the degree of blueness / basophilia

LAP SCORE KAPLOW COUNT

Decreased LAP score <10

CML VIRAL PAROXYSMAL

Increased LAP >100

Neutrophilic leukemoid reaction (bacterial infection) ● Polycythemia vera PV ● Myelofibrosis with myeloid metaplasia MMM ● Essential Thrombocythemia ● Third trimester pregnancy

used to differentiate myeloblasts and neutrophilic granulocytes from cells of monocytic origin.

esterase

Stable enzyme that last for months ● Can use old blood smears or anticoagulated blood

specific esterase: NASDCA

Stains esterases Chloroacetate esterase) present in the primary granules of granulocytes.

NASDCA

Myeloblasts and Auer Rods show a positive reaction. ● Bright red granules in cytoplasm of neutrophils, neutrophil precursors.

NASDCA

(+) Granulocytic cells

○ Blast cells ○ Precursor cells

(-) Monocytic cells

○ Monoblasts ○ Promonocytes acute monoblastic anemia

Uses air-dried blood or bone marrow smears or blood anticoagulated with EDTA or heparin.

ANAE, ANBE

Marker for monocytes, promonocytes, and monoblasts, megakaryocytes

ANAE

Nonspecific esterase stains monocytes (and monoblasts). ○ Inhibition by

sodium flouride

The addition of fluoride renders the monocytic cells (and blasts)

negative

more specific for monocytes (monoblasts, pronormoblasts, promonocytes) ○ Cannot stain megakaryocytes, platelets (unlike alpha-naphthyl acetate esterase)

Alpha-naphthyl butyrate esterase

Positive for specific esterases ★ Negative for non-specific esterases

Acute myeloid leukemia

Positive for both specific and non-specific esterase

acute myelomonocytic leukemia

Negative for specific esterase ★ Positive for non-specific esterase

monoblastic leukemia

Undifferentiated myeloid blasts ● AML minimally differentiated ● AML not otherwise categorized

FAB M0

Account for less than 5% of AML ● Auer rods are absent ● No clear evidence of cell maturation ● MPO (-), SBB (-) ○ Very young cells present ● CD13, CD33, CD34 , and CD117

Myeloblasts (predominate) and promyelocytes ● Predominate without further maturation of myeloid cells ● Can cause Chloroma: localized tumor masses consisting of myeloblasts

M1 without maturation

>30% blasts, <10% granulocytic cells, >90% Myeloblasts Auer rods are seen ● MPO (+), SBB (+) ○ At least 3% of blasts ● CD13, CD33, CD34, and CD117

Auer rods are seen ● MPO (+), SBB (+) ○ At least 3% of blasts ● CD13, CD33, CD34, and CD117

M1 without maturation

>30% blasts, > 10% granulocytic cells, <90% Myeloblasts

M2 WITH MATURATION

Auer rods are seen ● t12:21; RUNX1/ RUNX1T1 ○ A chromosomal abnormality in some cases

M2 WITH MATURATION

Most aggressive of acute leukemia

M3 PROMYELOCYTIC LEUKEMIA

>30% blasts, >10% granulocytic cells, <30% - 50% Promyelocytes ● Contain many Auer Rods

M3 PROMYELOCYTIC

cell w/ mass or bundles of Auer Rods ● t(15;17) PML/RARA:

FAGGOT CELLS IN M3 PROMYELOCYTIC

Therapy with all trans retinoic acid ATRA or simply retinoic acid.

M3 PROMYELOCYTIC

Naegeliʼs type of monocytic leukemia

M4 myelomonocytic

Myeloid antigens: CD13, CD33 ● Monocytic Antigens: CD14, CD4, CD11b, CD11c, and CD64 ● inv(16); t(16;16); CBFBMYH11

M4 myelomonocytic

A bone marrow aspiration reveals myeloblasts and monoblasts along with abnormal eosinophils

FABM4Eo: Acute Myelomonocytic Leukemia with Eosinophilia

cause the fusion of core binding factor beta-myosin heavy chain mutation CBFBMYH11.

INV 16 AND T(16;16) FAB M4

AML with inv(16) and t(16;16) with the fusion of CBFBMYH11.

Most cells are monocytic ○ More than 80% of the marrow cells are of monocytic origin

M5 MONOCYTIC

CD14, CD4, CD11b+, CD11c+, and CD64+ ● t(9;11); KMT2A (MLL) MLLT3

M5 MONOCYTIC

Large monoblasts 80% in bone marrow and peripheral blood ○ Schillingʼs type of Acute Leukemia

FAB M5a

Acute Monocytic leukemia, poorly differentiation (Acute Monoblastic)

FAB M5 POORLY, MONOBLASTIC

Acute Monocytic Leukemia, well differentiated Acute Monocytic)

FAB M5A WELL MONOCYTIC

Di Guglielmo syndrome, Erythemic myelosis, Pure Erythroid Leukemia - the only pure erythroid leukemia)

M6 ACUTE ERYTHROLEUKEMIA

> 80% of the bone marrow cells are ______, and > 30% are _______

erythroid proerythroblasts

M:E ratio decreases to between 1:2 to 1:4

M6 ACUTE ERYTHROLEUKEMIA

50% or more of the blasts are of megakaryocytic lineage ● Diagnosis requires the presence of at least 20% blasts, of which at least 50% must be of megakaryocyte origin,

M7 MEGAKARYOBLASTIC LEUKEMIA

CD41+,CD42b+, CD61+ ●(1;22); RBM15MKL1

M7 MEGAKARYOBLASTIC ANEMIA

are identified by immunostaining, using antibodies specific for cytoplasmic von Willebrand factor or platelet membrane antigens

MEGAKARYOBLASTS

leukemias with at least 20% blasts, multilineage dysplasia, a history of myelodysplastic syndrome MDS or MDS/myeloproliferative neoplasm MPN, or a specific MDS-associated cytogenetic abnormality

ACUTE MYELOID LEUKEMIA WITH MYELODYSPLASIA RELATED CHANGES 20% blasts

refers to extramedullary proliferation of blasts of one or more myeloid lineages that disrupts tissue architecture ● Tissues commonly affected include skin, gastrointestinal tract and lymph nodes

myeloid sarcoma

approximately 10% of newborns with Down syndrome present with transient ● abnormal myelopoiesis which is morphologically indistinguishable from AML ● among individuals with down syndrome, there is a 50x increased incidence of AML

MYELOID PRLOFERATION RELATED TI DOWN SYNDROME GATA1

rare clinically aggressive tumor derived from precursors of plasmacytoid dendritic cells ● Presents with skin lesion and may ultimately progress to involve peripheral blood and bone marrow

BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM

leukemia where there is no clear evidence of differentiation along a single cell line ● acute undifferentiated leukemias AULs

ACUTE LEUKEMIA OF AMBIGUOUS LINEAGE ALALs

demonstrate a multiplicity of antigens

MIXED PHENOTYPE ACUTE LEUKEMIAS

is the most common cancer in children

ACUTE LYMPHOBLASTIC LEUKEMIA ALL

12x the size of a lymphocyte, scant cytoplasm, coarse chromatin, deeply staining

SMALL LYMPHOBLASTS

23x the size of a lymphocyte, prominent nucleoli, membrane irregularities; confused with myeloblasts

large lymphoblasts

35x the size of a lymphocyte, with granules

myeloblasts

mostly involves T-cells

FAB L1

is the most common type of adult ALL

FAB L2

Philadelphia chromosome-positive ALL has the worst prognosis among ALLs ● More common in adults than in children

B-lymphoblastic leukemia/ lymphoma with the t(9;22); BCRABL1 mutation

A precursor lymphoid neoplasm which is composed of B-lymphoblasts and carries a translocation between the KMT2A gene at 11q23.3 and another gene partner resulting in the production of a KMT2A related fusion protein ● Common in very young infants; the translocation may even occur in utero ● This leukemia has a very poor prognosis

B-lymphoblastic leukemia/lymphoma with t(v;11q23; KMT2AMLL

About 25% of childhood ALL show this mutation ● In children, it carries an excellent prognosis with a cure rate of over 90%

B-lymphoblastic leukemia/lymphoma with t(12;21); ETV6RUNX1 translocation

common in childhood BALL accounting for 25% of cases. ● associated with a very favorable prognosis in children

B-lymphoblastic leukemia/lymphoma with Hyperdiploidy

conveys a poor prognosis

HYPODIPLOIDY

There is a de novo mutation ● It has the worst prognosis among all ALL

KMT2A t(v;11q23)

more than 46 chromosomes

HYPERDIPLOIDY

less than 46 chromosomes

HYPODIPLOIDY