Leukemias and Myeloid Disorders 1

Question 1

Leukemia defined

Answer 1

Neoplastic proliferation of hematopoeitic cells

Question 2

Lymphomas and leukemias

Answer 2

Can be caused by the same cell types

Lymphomas are solid neoplasms of lymphoid cells outside the marrow

Question 3

Leukemia leading cause of cancer death

Answer 3

In children/young adults

Question 4

Which are most common

Answer 4

Acute and chronic each half

AML most common acute, CLL most common chronic

Question 5

Sex and luekemia

Answer 5

Male mostly

Especially Hairy cell leukemia and T cell ALL

Question 6

Inherited genetic and chromosomal risk for leukemia

Answer 6

Down sydnrome

Fanconis anemia

Question 7

Radiation and drugs and leukemia

Answer 7

Radiation - increased risk of all except CLL

Drugs - alkylating agents, topoisomerase inhibitors increase risk of acute

Smoking increase AML risk

Question 8

Viral and leukemia

Answer 8

Human T cell leukemia virus and T cell leukemias/lymphomas

EBV or HHV-8

Question 9

Immune and leukemia

Answer 9

Chronic immune stimulation and immunodeficiency associated with increased risk

Question 10

Mutations (common)

Answer 10

t(9;22) - Philly - Most CML and some ALL

t(15;17) - in promyelotic AML (retinoic acid receptor fuses with PML…tx with trans-retinoic acid)

t(8;21) in AML with maturation (favorable)

in(16) in AML with myelomonocytic diff and abnormal eosinophils (favorable)

t(12;21) in favorable ALL

11q23 (MLL gene) infantile ALL t(4;11), some AML following topoisomerase inhibitors (bad prognosis)

Trisomy 8, momnosomey, of chromosomes 5 and 7 associated with AML and myelodisplastic disroders

Question 11

Acute vs chonirc leukemia

Answer 11

Acute - fatal…at least 20% blast cells…sudden onset…marked cytopenias and more symtpoms

Chronic - greater cell maturation…better survival…more prominent splenomegaly…more gradual symptoms and mild cytopenias

Question 12

Clinical manifestations

Answer 12

Bone marrow - neutropenia, thrombocytopenia, anemia

Organ infiltration

INcreased metab and cell lysis

Question 13

Bone
Lymphadenopathy
Splenomegaly

Types of leukemias

Answer 13

Bone pain, espeically in acute

LAD - in lymphoctyic anemias, mostly CLL

Spleno - Mild to mod in acute, mod in CLL, most in CML

Question 14

Hepato
CNS
Skin
Myeloid sarcomas and leuk

Answer 14

Hepato - most in CLL
CNS - espeically ALLs, some AMLs
Skin - T cell and monocytic leukemias
Mye Sarc- bone or soft tissue infiltrates in AML

Question 15

Cytochemistry used for

Answer 15

AML for most part

Question 16

Cytogenics used for

Answer 16

CML confirmatory…subtypes of acute

Question 17

ALL types

Answer 17

Precursor B or T lymphoblastic leukemia

Same cell may cause lymphoma but if 25% or more lymphoblasts in marrow then leukemia

Question 18

Most common patients with ALL

Answer 18

Children, adolescents (most common in childreN)

More in men

Question 19

ALL subtype and flow cytometry…also symptoms

Answer 19

Bone pain, CNS< tests
May have low white count

Precurosr T (15%) - Mediastinal mass or lymphoma common )…more common in males

Question 20

Prognosis, morphology of ALL

Answer 20

95% of childrne into remission

Round and convoluted nuclei, small to medium with little cytoplasm, high grwoth rate

Question 21

AML primary population

Answer 21

Most adults and more male

Question 22

AML classifcation

Answer 22

Need cytogenics 
Recurring cytogenic abn (8;21), t(15;17)
Mylodysplasia related changes
Therapy related
NOS

Question 23

AML onset

Answer 23

Gum hyperplasia (esp in monocytic)
DIC in promyelocytic, may be aleukemic

Question 24

Morphology and flow cytometry and prognosis of AML

Answer 24

Auer rods…positive nezym estains

60% remission but most relapse

Question 25

Favorable and unfavorable AML

Answer 25

Favorable - t(8;21), promyelocytic t(15;17), inv(16), isolated NPM 1 mutation Unfavorable - AML with myelodysplasia changes (del 5,7), therapy related AML, FLT3 mutations

Question 26

Acute promyelocytic leukemia

Answer 26

t(15;17) Abnormal RAR...can lead to DIC Look for multiple auer rods and intense granularity ATRA is the therpay

Question 27

Acute leukemia of ambiguous lineage

Answer 27

Primitive acute leukemias showing either insufficienct evidence of lymphoid or myeloid differentiation OR showing both myeloid and lymphoid or bothB and T cell differentiation Typically a poor prognosis

Question 28

B lymphoid-myeloid cases mutations

Answer 28

t(9;22) or 11q23 (MLL)

Question 29

CML mutation and ages

Answer 29

t(9;22) - Philly...c-abl transferred to bcr region of 22...increased tyrosine kinase activity...more cell division...doesn't block differentiation 26-60

Question 30

Symptoms of CML and what to look for

Answer 30

Splenomegaly Netutrophilia with less than 5% blasts and all stages of myeloid precursors...basophilia 100% cellular bone marrow with increased small MK but full granulocytic maturation Thrombocytosis in 50%

Question 31

CML blast phase

Answer 31

After about 3 years. Myeloid - 70% Lymphoid - 30%

Question 32

Effect of MLL mutation, BCR-ABL mutation and RAR mutation

Answer 32

MLL - increased self renewal BCR-ABL - increased growth and survival RAR - differentiation blocked

Question 33

Philly chromosome mutation and what it causes

Answer 33

CML and ALL | BCR-ABL fusion protein from t(9;22) is tyr kinase that activates pro-growht and survival

Question 34

t(15;17) mutation

Answer 34

AML (promyelocytci) | PML-RARE fusion creates abnormal RAR

Question 35

Core binding factor mutations

Answer 35

Disrupt TF needed (usually good prognosis) t(8;21) - AML with maturation inv (16) - monocytic AML with abnormal eosino t(12;21) - favorable ALL`

Question 36

MLL mutation

Answer 36

11q23 Poor Histone modifying protein that allows prolif pathways to be turned on

Question 37

Mature B cell and plasma cell markers

Answer 37

Kappa and lambda light chains

Question 38

First tier of AML diagnosis

Answer 38

Cytogenics

Question 39

In a nutshell

Answer 39

Is it acute leukemia (more than 20% blasts)...if yes then myeloid or lymphoid (flow)...if lymphoid, B or T (flow)...if myeloid, does it have recurring CG abnormality)..if not, then is there associated dysplasia or histroy of chemo or XRT...if not, is there maturation

Question 40

Things for good diagnosis of precurosr B cell ALL

Answer 40

Hyperdiploidy t(12;21) mutation Age 2-10 with lower WBCs at diagnosis

Question 41

Poor prognosis of B cell ALL

Answer 41

``` Hypodiploidy Under 1 or over 10 Higher WBC t(9;22) - BCR/ABL, Philly t(4;11) - AF4/MLL ```

Question 42

AML with maturation

Answer 42

t(8;21) good prognosis Core binding factor mutations

Question 43

Myelomonocytic AML

Answer 43

Inv (16) or t(16,16) | Abnormal eosinophils

Question 44

Monocytic AML

Answer 44

11q23 MLL abn | Poor prognosis

Question 45

Promyelocytic AML

Answer 45

t)15;17) Distinctive granules with Auer rods and DIC Good prognosis if treated

Question 46

NPM1, FLT-3 and CEBPA

Answer 46

In AML with normal CG, prognositc significance ``` FLT-3 duplication - bad NPM 1 - good CEBPA - good FLT3 plus NPM1 - IM FLT3 plus CEPBA - ? ```

Question 47

Alkylating agent and toposiomerase related changes

Answer 47

Alkylating - chr 5,7 loss Topo - 11q23