WBC 4: MDS; Acute Leukemias

what is the differentiating factor between SAA and VSAA?

<0.2 × 10⁹/L neutrophils

the following characteristics are characteristic of _____

• BM: hypocellular

• Neutrophils (x 10⁹/L): 0.5-1.5

• PLTs (x 10⁹/L): 20-50

• Other:

  • hemoglobin <10 g/dL

  • reticulocytes <30 × 10⁹/L

MAA

the following characteristics are characteristic of _____

• BM: hypocellular (<25%)

• Neutrophils (x 10⁹/L): 0.2-0.5

• PLTs (x 10⁹/L): <20

• Other:

  • reticulocytes <20 × 10⁹/L 

SAA

the following characteristics are characteristic of _____

• BM: hypocellular (<25%)

• Neutrophils (x 10⁹/L): <0.2

• PLTs (x 10⁹/L): <20

• Other:

  • reticulocytes <20 × 10⁹/L 

VSAA

acquired clonal hematopoietic disorders:

MDS

somatic gene mutation at the HSC level:

MDS

characterized by progressive cytopenias in the peripheral blood (reflecting defective maturation in erythroid, myeloid, megakaryocytic lines) and dyspoiesis in each line:

MDS

the following is associated with ____

• risk of development into AML

• median age of 76

MDS

the following are risk factors for ____

• old age (above 65)

• inherited BM failure syndromes such as Fanconi anemia, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome

MDS

these morphological abnormalities of the peripheral blood (top 2 images) and BM (bottom 2 images) are characteristic of ____.

dyserythropoiesis 

these morphological abnormalities of the peripheral blood are characteristic of ____.

dysmyelopoiesis 

these morphological abnormalities of the BM are characteristic of ____.

dysmyelopoiesis

these morphological abnormalities of the peripheral blood (top image) and BM (bottom 2 images) are characteristic of ____.

dysmegakaryopoiesis

immature myeloid/monocyte antigen marker:

CD64

the following are peripheral blood lab features of _____

• anemia in >85% cases

• high MCV

• poikilocytosis (oval, elliptical, teardrop, spheres, fragmented cells)

• neutropenia

• neutrophil hypogranularity

• acquired pelger huet

• ring-shaped nuclei in neutrophils

• mild to moderate thrombocytopenia

• large PLTs with poor granulation

MDS

the following are blood plasma lab features of _____

• serum iron, transferrin, ferritin, LDH, and uric acid are elevated 

MDS

the following are BM lab features of _____

• hypercellular in one or more lines with dysplasia

MDS

which MDS WHO classification is consistent with the following characteristics:

• anemia

• infection

• petechiae (depending on the lineage involved)

• <1% blasts in peripheral blood

• <5% blasts in BM

MDS-SLD

MDS-SLD refers to MDS with _____ dysplasia.

single lineage 

MDS-MLD refers to MDS with _____ dysplasia.

multilineage

which MDS WHO classification is consistent with the following characteristics:

• more than one lineage is dyspoietic

• <1% blasts in peripheral blood

• <5% blasts in BM

MDS-MLD

which MDS WHO classification is consistent with the following characteristics:

• SF3B1 (spliceosome) mutation

• at least 5% ring sideroblasts

• dimorphic RBC picture on PBS (combination of hypochromic and normochromic cells)

MDS-RS

what gene is associated with the spliceosome mutation in MDS-RS?

SF3B1

which MDS WHO classification is consistent with the following characteristics:

• trilineage cytopenia

MDS-EB

which type of MDS-EB is consistent with the following characteristics:

• 5-9% blasts in BM

• 2-4% blasts in peripheral blood

MDS-EB1

which type of MDS-EB is consistent with the following characteristics:

• 10-19% blasts in BM

• 5-19% blasts in peripheral blood

MDS-EB2

which MDS WHO classification is consistent with the following characteristics:

• affects predominantly women

• occurs at a median age of 70

• patients have anemia without other cytopenias 

MDS with isolated del(5q)

MDS with isolated del(5q) is also referred to as:

5q syndrome

if there are not enough specific characteristics that align with WHO classifications of we can classify the MDS as ____.

MDS, unclassifiable

what is a major indication of MDS in peripheral blood and BM?

a. dyspoiesis

b. leukocytosis with left shift

c. normal BM with abnormal peripheral blood features

d. thrombocytosis

dyspoiesis

an alert hematologist should recognize all the following peripheral blood abnormalities as diagnostic clues in MDS EXCEPT:

a. oval macrocytes

b. target cells

c. agranular neutrophils

d. circulating micromegakaryocytes

target cells 

a patient has anemia, oval macrocytes, and hypersegmented neutrophils. which of the following tests would be most efficient in differential diagnosis of this disorder?

a. serum iron and ferritin levels 

b. erythropoietin level 

c. vitamin B12 and folate levels

d. chromosome analysis 

vitamin B12 and folate levels 

FAB mostly considered _____ while WHO is more informative, and considers clinical features, morphology, immunophenotyping, cytogenetics, and molecular genetics.

morphology

what B-ALL translocation is associated with the gene BCR-ABL1?

t(9;22)

what B-ALL translocation is associated with the gene KMTA2 (MLL) rearranged?

t(v;11q23.3)

what B-ALL translocation is associated with the gene TEL-AML1 (ETV6-RUNX1)?

t(12;21)

which gene is associated with t(9;22)?

BCR-ABL1

which gene is associated with t(v;11q23.3)?

KMT2A (MLL) rearranged

which gene is associated with t(12;21)?

TEL-AML1 (ETV6-RUNX1)

in ____, the cytogenetic alterations show less specificity and less correlation with the prognosis and treatment outcome than in B-ALL.

T-ALL

which B-lymphoblastic leukemia/lymphoma is associated with the following:

• worst prognosis

• philadelphia chromosome (+)

• more common in adults

• responds to imatinib (Gleevec)

a. t(9;22)(q34.1;q11.2);BCR-ABL1

b. t(v;11q23.3); KMT2A (MLL) rearranged

c. t(12;21)(p13.2;q22.1); TEL-AML1 (ETV6-RUNX1)

d. with hyperdiploidy

e. with hypodiploidy

a

which B-lymphoblastic leukemia/lymphoma is associated with the following:

• more common in very young adults

• translocation may occur in utero

• very poor prognosis

a. t(9;22)(q34.1;q11.2);BCR-ABL1

b. t(v;11q23.3); KMT2A (MLL) rearranged

c. t(12;21)(p13.2;q22.1); TEL-AML1 (ETV6-RUNX1)

d. with hyperdiploidy

e. with hypodiploidy

b

which B-lymphoblastic leukemia/lymphoma is associated with the following:

• rare in adults

• excellent prognosis in children 

  • cure rate of over 90%

a. t(9;22)(q34.1;q11.2);BCR-ABL1

b. t(v;11q23.3); KMT2A (MLL) rearranged

c. t(12;21)(p13.2;q22.1); TEL-AML1 (ETV6-RUNX1)

d. with hyperdiploidy

e. with hypodiploidy

c

which B-lymphoblastic leukemia/lymphoma is associated with the following:

• less common in adults

• favorable prognosis in children

a. t(9;22)(q34.1;q11.2);BCR-ABL1

b. t(v;11q23.3); KMT2A (MLL) rearranged

c. t(12;21)(p13.2;q22.1); TEL-AML1 (ETV6-RUNX1)

d. with hyperdiploidy

e. with hypodiploidy

d

which B-lymphoblastic leukemia/lymphoma is associated with the following:

• poor prognosis in both children and adults

a. t(9;22)(q34.1;q11.2);BCR-ABL1

b. t(v;11q23.3); KMT2A (MLL) rearranged

c. t(12;21)(p13.2;q22.1); TEL-AML1 (ETV6-RUNX1)

d. with hyperdiploidy

e. with hypodiploidy

e

FAB classification that refers to small blasts with a thin rim of cytoplasm:

pre B ALL (L1)

FAB classification that refers to irregular clefts of the nucleus

T cell ALL (L2)

FAB classification that refers to burkitt leukemia with vacuolations:

mature B cell ALL (L3)

the following immunophenotype refers to which ALL subtype:

• CD34 +

• CD19 +

• cytoplasmic CD22 +

• TdT +

early (pro/pro-pre) B-ALL

the following immunophenotype refers to which ALL subtype:

• CD34 +

• CD19 +

• CD10 +

• cytoplasmic CD22 +

• TdT +

intermediate (common) B-ALL

the following immunophenotype refers to which ALL subtype:

• CD34 -

• CD19 +

• cytoplasmic CD22 +

• cytoplasmic µ +

• TdT +

pre B ALL

the following immunophenotype refers to which ALL subtype:

• CD2 +

• CD3 +

• CD4 +

• CD5 +

• CD7 +

• CD8 +

• TdT +

T ALL

_____ is seen most often in teenage males with

• mediastinal mass

• elevated peripheral blast counts

• meningeal involvement

• infiltration of extra marrow sites

T ALL

most common type of leukemia in adults, less common in children:

AML

the following lab findings are consistent with ____

• >90% show blasts in peripheral blood

• WBC between 5-30 × 10³/uL

• anemia

• thrombocytopenia 

• neutropenia (WBC could be normal but anemia and thrombocytopenia are always present)

AML

the following lab findings are consistent with ____

• BM hypercellular with >20% blasts (not enough without specific genetic abnormalities)

• serum chemical analysis

  • hyperuricemia 

  • hyperphosphatemia

  • hypocalcemia

  • risk of acute renal failure

  • tumor lysis syndrome (in case of very high WBC)

AML

the most significant different between FAB and WHO classifications of AML is that FAB requires _____% blasts while WHO requires >20% blasts.

>30%

for AML, which translocation is associated with the gene RUNX1-RUNX1T1?

t(8;21)

for AML, which translocation is associated with the gene CBFB-MYH11?

t(16;16) OR inv(16)

for AML, which translocation is associated with the gene PML-RARA?

t(15;17)

for AML, which translocation is associated with the gene KMT2A (MLL)-MLLT3?

t(9;11)

which gene is associated with the following AML translocation: t(8;21)?

RUNX1-RUNX1T1

which gene is associated with the following AML translocation: t(16;16) aka inv(16)?

CBFB-MYH11

which gene is associated with the following AML translocation: t(15;17)?

PML-RARA

which gene is associated with the following AML translocation: t(9;11)?

KMT2A (MLL)-MLLT3

AML with mutated NPM1 is mostly in ____ leukemias with good prognosis?

monocytic

AML with biallelic mutation of CEBPA has a poor prognosis. true or false?

false

AML with mutated RUNX1 has the worst overall survival. true or false?

true

which FAB classification of AML refers to acute myeloid leukemia with minimal differentiation (*BLASTS! no maturity)?

M0

which FAB classification of AML refers to acute myeloid leukemia without maturation?

M1

which FAB classification of AML refers to acute myeloid leukemia with maturation?

M2

which FAB classification of AML refers to acute promyelocytic leukemia?

M3

which FAB classification of AML refers to acute myelomonocytic leukemia?

M4

which FAB classification of AML refers to acute myelomonocytic leukemia with eosinophilia?

M4eo

which FAB classification of AML refers to acute monocytic leukemia with poor differentiation?

M5a

which FAB classification of AML refers to acute monocytic leukemia that are well differentiated?

M5b

which FAB classification of AML refers to acute erythroleukemia?

M6

which FAB classification of AML refers to acute megakaryocytic leukemia?

M7

which AML translocation is associated with the following information:

• 5% of AML cases

• predominantly in children and young children

• myeloblasts with dysplatic granular cytoplasm, auer rods, and some maturation (similar to FAB M2 phenotype)

• pseudo-pelger-huet cells and hypogranulation 

• eosinophilia may be seen 

• this diagnosis of the subtype is based on the genetic abnormality, regardless of blast count

t(8;21)

which AML translocation is associated with the following information:

• 5-8% of AML cases

• myeloblasts, monoblasts, and promyelocytes in peripheral blood and BM

• eosinophilia with dysplastic changes may be seen in BM

• CNS involvement (relapse)

• the genetic aberration is sufficient for diagnosis regardless of blast count

t(16;16) OR inv(16)

which AML translocation is associated with the following information:

• 5-10% of AML cases

• differentiation block at pro stage 

• abnormal hypergranular promyelocytes, some with auer rods (sometimes bundle of auer rods, aka faggot cells)

• risk of DIC (release of procoagulant from promyelocytes)

• a microgranular variant (30-40% of APL cases), may be confused with other AML types (figure B) 

• unique treatment: all-trans-retinoic acid (ATRA) and arsenic trioxide 

  • ATRA induces differentiation of promyelocytes

• the genetic aberration is sufficient for diagnosis regardless of blast count

t(15;17)

which condition has the unique treatment of all-trans-retinoic acid (ATRA) and arsenic trioxide?

APL

which AML translocation is associated with the following information:

• 6% of AML cases

• increase in monoblasts and immature monocytes 

• blasts are large with abundant cytoplasm and fine nuclear chromatin 

• blasts may have pseudopodia, granules and vacuoles

• typically in children

• skin and gum involvement may occur

t(9;11)

which FAB classification is associated with the following information?

• CD13 +

• CD33 +

• CD34 +

• CD117 +

M0; M1

which FAB classification is associated with the following information?

• MPO negative

• SBB negative

M0

which FAB classification is associated with the following information?

• <5% of cases

• infants or older patients 

M0

which FAB classification is associated with the following information?

• MPO and SBB positive in 3% of blasts

M1

which FAB classification is associated with the following information?

• blasts 90% of non-erythroid cells in BM

• <10% of cells show maturation up to myeloctes

M1

which FAB classification is associated with the following information?

• blasts >20% in the BM 

• >10% maturing neutrophil lineage cells 

• <10% of blasts of the monocytic lineage 

M2

which FAB classification is associated with the following information?

• CD34 +

• CD13 +

• CD15 +

• CD11b +

• HLA-DR +

• negative for monocytic markers: CD36, CD14, CD64

M2

CD36, CD14, CD64 refer to ____ markers.

monocytic

which FAB classification is associated with the following information?

• differentiation block at the promyelocyte stage 

• risk of DIC 

M3

which FAB classification is associated with the following information?

• CD34 -

• CD13 +

• CD33 +

• CD64 +

• CD11b -

• HLA-DR -

M3

which FAB classification is associated with the following information?

• very high WBC count

• presence of monocytic cells (monoblasts and promonocytes)

• positive naphthol-AS-D chloroacetate esterase (specific stain)

M4

which FAB classification is associated with the following information?

• CD13 +

• CD33 +

• CD64 +

• CD14 +

• CD4 +

• CD11c +

M4

which FAB classification is associated with the following information?

• CD14 +

• CD4 +

• CD64 +

• CD11c +

• CD11b +

M5

what cell predominates in M5a?

monoblasts 

what cell predominates in M5b?

promonocytes

which FAB classification is associated with the following information?

• positive alpha-naphthyl butyrate esterase (nonspecific) esterase stain

M5

which FAB classification is associated with the following information?

• >80% of cells are of erythroid origin

• >30% are pro-normoblasts

• dysplastic changes in erythroid precursors such as multinucleation (N:C asynchrony, vacuolization)

• >50% nRBCs on PBS

• ringed sideroblasts, HJ bodies

• aggressive and rapid clinical course

M6