A 62-year-old man who has never had chemotherapy or radiotherapy presents with fatigue; he has no earlier blood disorder. Hemoglobin 84 g/L (8.4 g/dL), WBC 7.2 × 10^9/L with 18% blasts, platelets 520 × 10^9/L (reference 150-450). The marrow has 34% myeloblasts (CD34+, CD117+, CD13+, CD33+, HLA-DR+, MPO+ in a minority), many small megakaryocytes with one or two nuclear lobes, and dysplastic granulocytes. Karyotype: 45,XY,inv(3)(q21.3q26.2),-7[18]/46,XY[2]. NPM1, CEBPA and FLT3 are not mutated. Under the WHO 5th edition, what is the correct classification?

Acute megakaryoblastic leukemia

Essential thrombocythemia in blast phase

A 3-day-old boy with Down syndrome has an enlarged liver. CBC: WBC 64 × 10^9/L with 42% blasts, hemoglobin 182 g/L (18.2 g/dL), platelets 96 × 10^9/L. The blasts have basophilic cytoplasm with small surface blebs and are myeloperoxidase negative. Flow cytometry: CD34+, CD117+, CD33+, CD41+, CD61+, CD7+, HLA-DR negative, and B- and T-lymphoid markers negative. Sequencing finds a GATA1 mutation, and the karyotype shows only constitutional trisomy 21. Blood cultures are negative, and he is feeding well. The best classification is:

Transient abnormal myelopoiesis

Myeloid leukemia of Down syndrome

Neonatal leukemoid reaction to sepsis

Congenital B-lymphoblastic leukemia

A 66-year-old has pancytopenia. Erythroid precursors make up 88% of marrow cells, and 40% of all marrow cells are proerythroblasts that are PAS positive and express CD71 and E-cadherin. These cells are MPO negative, B12 and folate are normal, and TP53 is mutated. Under the WHO 5th edition, the diagnosis is:

Acute megakaryoblastic leukemia

Acute leukemias

26 DOH Abu Dhabi (HAAD) lab licensing practice questions on Acute leukemias, part of Hematology. The first 25 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 62-year-old man who has never had chemotherapy or radiotherapy presents with fatigue; he has no earlier blood disorder. Hemoglobin 84 g/L (8.4 g/dL), WBC 7.2 × 10^9/L with 18% blasts, platelets 520 × 10^9/L (reference 150-450). The marrow has 34% myeloblasts (CD34+, CD117+, CD13+, CD33+, HLA-DR+, MPO+ in a minority), many small megakaryocytes with one or two nuclear lobes, and dysplastic granulocytes. Karyotype: 45,XY,inv(3)(q21.3q26.2),-7[18]/46,XY[2]. NPM1, CEBPA and FLT3 are not mutated. Under the WHO 5th edition, what is the correct classification?
1. AAML, myelodysplasia-related
2. BAcute megakaryoblastic leukemia
3. CAML with MECOM rearrangement
4. DEssential thrombocythemia in blast phase
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Answer: C · AML with MECOM rearrangement
The inv(3)(q21.3q26.2) moves a GATA2 enhancer next to MECOM, and AML with MECOM rearrangement is one of the WHO 5th edition's AML types with a defining genetic abnormality. These types take precedence over AML, myelodysplasia-related, so the monosomy 7 and the dysplasia do not change the classification, although they add to an already poor prognosis. A normal or raised platelet count with small, hypolobated megakaryocytes is characteristic of this leukemia. Acute megakaryoblastic leukemia needs at least half of the blasts to be megakaryoblasts (CD41 or CD61 positive), whereas these blasts are myeloblasts. Essential thrombocythemia in blast phase would need an earlier myeloproliferative neoplasm, and he has none.
- A: Defining genetic abnormalities such as a MECOM rearrangement take precedence over myelodysplasia-related changes.
- B: The blasts are myeloblasts; the small megakaryocytes are mature dysplastic forms, not blasts.
- D: He has no earlier myeloproliferative neoplasm, and thrombocytosis is a feature of this AML.
Question 2 · Hard
A 4-year-old girl has pallor, bruising and bone pain. WBC 11 × 10^9/L with 38% blasts, hemoglobin 74 g/L (7.4 g/dL), platelets 31 × 10^9/L. Marrow blasts are 86%: small cells with scant cytoplasm, negative for myeloperoxidase and Sudan black B. Flow cytometry: CD19+, CD10 bright, CD34+, TdT+, cytoplasmic CD79a+, CD20 negative, with CD13 and CD33 on most blasts; cytoplasmic CD3, MPO, CD14 and CD64 negative. The G-banded karyotype is 46,XX in all 20 metaphases. Which recurrent genetic abnormality is most likely, despite the normal karyotype?
1. AETV6::RUNX1 from t(12;21)
2. BBCR::ABL1 from t(9;22)
3. CTCF3::PBX1 from t(1;19)
4. DKMT2A::AFF1 from t(4;11)
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Answer: A · ETV6::RUNX1 from t(12;21)
The blasts are precursor B cells (CD19, CD10, CD34, TdT, cytoplasmic CD79a), so this is B-lymphoblastic leukemia; CD13 and CD33 do not change the lineage when MPO and monocytic markers are negative. In a child aged 1-10 years with a modest WBC, ETV6::RUNX1 is one of the two commonest genetic subgroups (with high hyperdiploidy, which the karyotype would show), and its blasts often express CD13 and CD33. The t(12;21)(p13.2;q22.1) exchanges chromosome ends with similar banding, so it is cryptic on G-banding and is found by FISH or RT-PCR, which is why new B-ALL is routinely tested with FISH or molecular panels. BCR::ABL1, KMT2A::AFF1 and TCF3::PBX1 come from translocations that are visible on a routine karyotype, and KMT2A::AFF1 is typical of infants with CD10-negative blasts. ETV6::RUNX1 carries a favorable prognosis.
- B: The Philadelphia chromosome of t(9;22) is visible on a routine karyotype.
- C: t(1;19) is visible on karyotype and usually seen in pre-B blasts with cytoplasmic mu chains.
- D: t(4;11) is visible on karyotype and typical of infants with CD10-negative blasts.
Question 3 · Hard
A 3-day-old boy with Down syndrome has an enlarged liver. CBC: WBC 64 × 10^9/L with 42% blasts, hemoglobin 182 g/L (18.2 g/dL), platelets 96 × 10^9/L. The blasts have basophilic cytoplasm with small surface blebs and are myeloperoxidase negative. Flow cytometry: CD34+, CD117+, CD33+, CD41+, CD61+, CD7+, HLA-DR negative, and B- and T-lymphoid markers negative. Sequencing finds a GATA1 mutation, and the karyotype shows only constitutional trisomy 21. Blood cultures are negative, and he is feeding well. The best classification is:
1. ATransient abnormal myelopoiesis
2. BMyeloid leukemia of Down syndrome
3. CNeonatal leukemoid reaction to sepsis
4. DCongenital B-lymphoblastic leukemia
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Answer: A · Transient abnormal myelopoiesis
The blasts are megakaryoblasts (CD41 and CD61 positive, cytoplasmic blebs, MPO negative) with aberrant CD7, and together with a GATA1 mutation and trisomy 21 in a newborn they define transient abnormal myelopoiesis (TAM). TAM affects about 10% of babies with Down syndrome, appears in the first days or weeks of life and resolves without chemotherapy within about 3 months in most babies, so the usual plan is supportive care and monitoring, not induction. Myeloid leukemia of Down syndrome has the same blast phenotype and GATA1 mutation but appears later, usually before age 5 and often after a myelodysplastic phase; about 1 in 5 babies with TAM go on to develop it. A leukemoid reaction shows maturing neutrophils rather than megakaryoblasts, and the lymphoid markers are negative.
- B: Myeloid leukemia of Down syndrome appears later in early childhood, not in the first days of life.
- C: A leukemoid reaction shows maturing neutrophils, not CD41- and CD61-positive blasts.
- D: The blasts are megakaryoblasts, and the lymphoid markers are negative.
Question 4 · Medium
In most Philadelphia chromosome-positive B-lymphoblastic leukemias, the BCR::ABL1 fusion protein is:
1. Ap145
2. Bp230
3. Cp190
4. Dp210
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Answer: C · p190
In Ph-positive B-ALL the break in BCR usually falls in the minor breakpoint region, which gives a 190 kDa fusion protein. Chronic myeloid leukemia usually has the major breakpoint and a 210 kDa protein, which is also found in a minority of Ph-positive ALL. The rare p230 form is linked to a neutrophil-predominant CML. Molecular assays must detect the right transcript, or a p190 case can be missed.
- A: About 145 kDa is the size of the normal ABL1 protein, not the fusion.
- B: p230 is a rare form linked to neutrophil-predominant CML.
- D: p210 is the usual CML protein and is found in only a minority of Ph-positive ALL.
Question 5 · Hard
A 66-year-old has pancytopenia. Erythroid precursors make up 88% of marrow cells, and 40% of all marrow cells are proerythroblasts that are PAS positive and express CD71 and E-cadherin. These cells are MPO negative, B12 and folate are normal, and TP53 is mutated. Under the WHO 5th edition, the diagnosis is:
1. AMegaloblastic anemia
2. BMDS with increased blasts
3. CAcute megakaryoblastic leukemia
4. DAcute erythroid leukemia
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Answer: D · Acute erythroid leukemia
WHO 5th edition defines acute erythroid leukemia by erythroid predominance, usually 80% or more of marrow cells, with at least 30% proerythroblasts, and most cases carry TP53 mutations. The proerythroblasts are MPO negative, express CD71 and E-cadherin, and are often PAS positive; glycophorin A (CD235a) appears as they mature. Normal B12 and folate exclude megaloblastic anemia, which can also give a large, immature erythroid marrow. Myeloblasts may be few, so a myeloblast count alone can miss the diagnosis.
- A: Normal B12 and folate exclude megaloblastic anemia.
- B: With 30% or more proerythroblasts and erythroid predominance, the case meets the erythroid leukemia criteria rather than MDS.
- C: Megakaryoblasts express CD41 and CD61, not CD71 and E-cadherin.
Question 6 · Medium
A marrow smear left unstained for several weeks gives weak myeloperoxidase staining. Which stain gives similar lineage information and stays reliable on older smears?
1. AAlpha-naphthyl butyrate esterase
2. BSudan black B
3. CPeriodic acid-Schiff
4. DPrussian blue
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Question 7 · Hard
A 6-year-old in remission from B-ALL has a marrow 4 weeks after a chemotherapy block. Flow cytometry finds 7% CD19-positive precursors with a smooth, continuous spread of CD34, CD10, CD20 and CD45 expression that follows the normal maturation pattern. These cells are most likely:
1. ARelapsed B-lymphoblastic leukemia
2. BHematogones from marrow regeneration
3. CA new T-lymphoblastic leukemia
4. DContaminating mature B cells from blood
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Question 8 · Medium
Monocytic differentiation in AML blasts is best shown by the flow cytometry markers:
1. ACD19, CD22 and CD79a
2. BCD41, CD61 and CD42b
3. CCD14, CD64 and CD11b
4. DCD71 and CD235a
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Question 9 · Hard
Two days after starting induction for B-ALL with a presenting WBC of 180 × 10^9/L, a 40-year-old's plasma (not hemolyzed) shows: potassium 6.3 mmol/L, phosphate 2.8 mmol/L (8.7 mg/dL), calcium 1.65 mmol/L (6.6 mg/dL), uric acid 690 µmol/L (11.6 mg/dL), creatinine rising and CK normal (reference: potassium 3.5 to 5.1 mmol/L, phosphate 0.8 to 1.5 mmol/L, calcium 2.15 to 2.55 mmol/L, uric acid 200 to 430 µmol/L). These results indicate:
1. AEDTA contamination of the sample
2. BTumor lysis syndrome
3. CPseudohyperkalemia from leukocytosis
4. DRhabdomyolysis
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Question 10 · Easy
Coarse block positivity in many lymphoblasts is a typical reaction with:
1. APeriodic acid-Schiff (PAS)
2. BSudan black B
3. CMyeloperoxidase
4. DNaphthol AS-D chloroacetate esterase
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Question 11 · Medium
By the classic cytochemical rule, an acute leukemia is called myeloid when myeloperoxidase or Sudan black B is positive in at least what proportion of blasts?
1. A20%
2. B10%
3. C50%
4. D3%
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Question 12 · Medium
In newly diagnosed AML, which molecular result should be available within a few days because it changes the induction regimen?
1. ATET2 mutation status
2. BBCR::ABL1 kinase domain mutations
3. CFLT3 mutation status
4. DJAK2 V617F status
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Question 13 · Medium
Under the NCI criteria, which presenting features place a child with B-lymphoblastic leukemia in the standard-risk group?
1. AAge under 1 year and WBC below 50 × 10^9/L
2. BAny age with a WBC below 100 × 10^9/L
3. CAge 1 to 9 years and WBC below 50 × 10^9/L
4. DAge 10 to 15 years and WBC below 100 × 10^9/L
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Question 14 · Hard
Leukemic blasts are myeloperoxidase positive in 45% of cells by flow cytometry and also show strong cytoplasmic CD3, with CD7 and CD34. B-cell markers are negative and no defining genetic abnormality is found. The best classification is:
1. AEarly T-cell precursor lymphoblastic leukemia
2. BT-ALL with aberrant myeloid antigens
3. CAML with aberrant CD7 expression
4. DMixed-phenotype acute leukemia, T/myeloid
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Question 15 · Hard
Blasts make up 78% of marrow cells. Fewer than 3% are positive for myeloperoxidase or Sudan black B, and nonspecific esterase is negative. Flow cytometry: CD34+, HLA-DR+, CD13+, CD33+, CD117+, cytoplasmic CD3−, CD19−, cytoplasmic CD79a−, MPO negative. Genetic tests show no defining or myelodysplasia-related abnormality. The best classification is:
1. AAcute undifferentiated leukemia
2. BB-lymphoblastic leukemia
3. CAML without maturation
4. DAML with minimal differentiation
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Question 16 · Medium
Under the WHO 5th edition, which finding on its own qualifies an AML with 20% or more blasts as myelodysplasia-related?
1. AA FLT3 internal tandem duplication
2. BDysplasia in 50% of cells of two lineages
3. CAn SRSF2 mutation
4. DAn NPM1 mutation
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Question 17 · Medium
In the WHO 5th edition, which of these AML types can be diagnosed with fewer than 20% blasts?
1. AAML with CEBPA mutation
2. BAML with maturation
3. CAML with BCR::ABL1 fusion
4. DAML with KMT2A rearrangement
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Question 18 · Easy
A flow cytometry tube for TdT needs a fix-and-permeabilize step, because this marker sits in the:
1. ANuclei of most lymphoblasts
2. BCytoplasm of monoblasts
3. CPrimary granules of myeloblasts
4. DSurface membrane of mature B cells
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Question 19 · Hard
Blasts from a 19-year-old have this phenotype: cytoplasmic CD3+, CD7+, CD1a−, CD8−, CD5 weak, CD34+, CD117+, HLA-DR+, CD13+, MPO negative. The best classification is:
1. AAML with minimal differentiation
2. BMixed-phenotype acute leukemia, T/myeloid
3. CCortical T-lymphoblastic leukemia
4. DEarly T-cell precursor lymphoblastic leukemia
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Question 20 · Medium
Which karyotype finding carries a poor prognosis in childhood B-lymphoblastic leukemia?
1. AHigh hyperdiploidy of 51 to 65 chromosomes
2. BTrisomies of chromosomes 4 and 10
3. CHypodiploidy with fewer than 44 chromosomes
4. Dt(12;21) ETV6::RUNX1
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Question 21 · Hard
A 30-year-old has bruising and WBC 86 × 10^9/L. Most cells have bilobed, folded nuclei and few visible granules. MPO is strongly positive in nearly all of them, nonspecific esterase is negative, fibrinogen is 0.9 g/L (90 mg/dL; reference 2.0 to 4.0 g/L) and D-dimer is high. The most likely diagnosis is:
1. AAML with maturation
2. BAPL, microgranular variant
3. CAcute monocytic leukemia
4. DAcute myelomonocytic leukemia
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Question 22 · Easy
Which marker is most specific for assigning acute leukemia blasts to the T lineage?
1. ACytoplasmic CD3
2. BSurface CD7
3. CSurface CD34
4. DNuclear TdT
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Question 23 · Easy
Gum swelling and skin infiltrates at diagnosis are most typical of which acute leukemia?
1. AAcute promyelocytic leukemia
2. BAcute monocytic leukemia
3. CB-lymphoblastic leukemia
4. DAML with minimal differentiation
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Question 24 · Medium
In AML with RUNX1::RUNX1T1, t(8;21), the myeloblasts often aberrantly express:
1. ACD19
2. BCytoplasmic CD3
3. CCD20
4. DCD5
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Question 25 · Hard
A 500-cell marrow differential in a suspected monocytic leukemia counts 35 myeloblasts, 40 monoblasts, 30 promonocytes and 60 mature monocytes; the rest are other cells. What is the blast percentage for WHO classification?
1. A15%, below the 20% threshold
2. B7%, below the 20% threshold
3. C33%, which meets the 20% threshold
4. D21%, which meets the 20% threshold
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Acute leukemias

In most Philadelphia chromosome-positive B-lymphoblastic leukemias, the BCR::ABL1 fusion protein is:

A marrow smear left unstained for several weeks gives weak myeloperoxidase staining. Which stain gives similar lineage information and stays reliable on older smears?

A 6-year-old in remission from B-ALL has a marrow 4 weeks after a chemotherapy block. Flow cytometry finds 7% CD19-positive precursors with a smooth, continuous spread of CD34, CD10, CD20 and CD45 expression that follows the normal maturation pattern. These cells are most likely:

Monocytic differentiation in AML blasts is best shown by the flow cytometry markers:

Coarse block positivity in many lymphoblasts is a typical reaction with:

By the classic cytochemical rule, an acute leukemia is called myeloid when myeloperoxidase or Sudan black B is positive in at least what proportion of blasts?

In newly diagnosed AML, which molecular result should be available within a few days because it changes the induction regimen?

Under the NCI criteria, which presenting features place a child with B-lymphoblastic leukemia in the standard-risk group?

Leukemic blasts are myeloperoxidase positive in 45% of cells by flow cytometry and also show strong cytoplasmic CD3, with CD7 and CD34. B-cell markers are negative and no defining genetic abnormality is found. The best classification is:

Under the WHO 5th edition, which finding on its own qualifies an AML with 20% or more blasts as myelodysplasia-related?

In the WHO 5th edition, which of these AML types can be diagnosed with fewer than 20% blasts?

A flow cytometry tube for TdT needs a fix-and-permeabilize step, because this marker sits in the:

Blasts from a 19-year-old have this phenotype: cytoplasmic CD3+, CD7+, CD1a−, CD8−, CD5 weak, CD34+, CD117+, HLA-DR+, CD13+, MPO negative. The best classification is:

Which karyotype finding carries a poor prognosis in childhood B-lymphoblastic leukemia?

Which marker is most specific for assigning acute leukemia blasts to the T lineage?

Gum swelling and skin infiltrates at diagnosis are most typical of which acute leukemia?

In AML with RUNX1::RUNX1T1, t(8;21), the myeloblasts often aberrantly express:

A 500-cell marrow differential in a suspected monocytic leukemia counts 35 myeloblasts, 40 monoblasts, 30 promonocytes and 60 mature monocytes; the rest are other cells. What is the blast percentage for WHO classification?