Acute Leukemias — MCQs
A 55-year-old male with fatigue and a palpable spleen is found to have a high white cell count predominantly consisting of mature lymphocytes. What is the most likely diagnosis?
What is the cell of origin of B-cell Acute Lymphoblastic Leukemia (B-ALL)?
In the context of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), which of the following cytogenetic abnormalities is associated with the worst prognosis?
Specific stain for myeloblasts is
Which of the following is used to detect abnormal gene sequences EXCEPT?
Among the following AML subtypes, non-specific esterase (NSE) staining is typically NEGATIVE in which one?
What is the most common type of acute myeloid leukemia in patients with Down's syndrome?
BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?
A bone marrow aspirate shows blast cells with multiple Auer rods arranged in bundles ('faggot cells'). Which molecular finding would confirm acute promyelocytic leukemia?
Myeloid sarcoma, which is a tumor mass consisting of myeloid blasts occurring at anatomic sites other than the bone marrow, is often characterized by chromosome aberrations. Which of the following is NOT typically associated with myeloid sarcoma?
Acute Leukemias Indian Medical PG Practice Questions and MCQs
Question 1: A 55-year-old male with fatigue and a palpable spleen is found to have a high white cell count predominantly consisting of mature lymphocytes. What is the most likely diagnosis?
- A. Acute lymphoblastic leukemia
- B. Chronic lymphocytic leukemia (Correct Answer)
- C. Myelodysplastic syndrome (ineffective hematopoiesis and cytopenias)
- D. Hairy cell leukemia (characterized by "hairy" appearing cells)
Explanation: ***Chronic lymphocytic leukemia*** - The presence of **fatigue**, a **palpable spleen**, and an elevated white cell count predominantly consisting of **mature lymphocytes** is highly characteristic of CLL [1]. - CLL is a common leukemia in older adults, where **monoclonal B-lymphocytes** accumulate in the blood, bone marrow, and lymphoid organs [1]. *Acute lymphoblastic leukemia* - This leukemia typically presents with **immature lymphocytes (blasts)** and a more aggressive clinical course, often seen in children [2]. - While it causes fatigue and can lead to organomegaly, the predominance of **mature lymphocytes** in the peripheral blood rules out ALL [2]. *Myelodysplastic syndrome (ineffective hematopoiesis and cytopenias)* - This syndrome is characterized by **ineffective hematopoiesis** and **cytopenias** (low blood cell counts), rather than a high white cell count. - It involves dysplasia in one or more myeloid cell lines, and the peripheral smear would show abnormal cell morphology, not a predominance of mature lymphocytes. *Hairy cell leukemia (characterized by "hairy" appearing cells)* - While it presents with **splenomegaly** and can cause fatigue, the characteristic cells have **"hairy" cytoplasmic projections** and are rarely found in high numbers in the peripheral blood initially. - The diagnosis is confirmed by flow cytometry and bone marrow biopsy, and the classic picture often includes **pancytopenia**, not just a high white cell count from mature lymphocytes.
Question 2: What is the cell of origin of B-cell Acute Lymphoblastic Leukemia (B-ALL)?
- A. T cells
- B. Immature B cells (Correct Answer)
- C. Immature T cells
- D. Both T & B cells
Explanation: ***Immature B cells*** - B acute lymphoblastic leukemia (B ALL) is primarily derived from the **malignant transformation of precursor B lymphocytes** [1]. - The disease is characterized by the presence of **immature B cell blasts** in the bone marrow and peripheral blood [1]. *T cells* - T cells are involved in a different lineage of leukemia known as T-ALL, not B ALL [1]. - The pathophysiology of B ALL specifically relates to **B cell precursors**, not T cell involvement. *Both T & B cells* - This option is incorrect as B ALL specifically originates from **B cell lineage**, and T cells are unrelated to its pathogenesis [1]. - The presence of both T and B cells together characterizes mixed lineage leukemias, which is not the case here. *Immature T cells* - Immature T cells are precursors for **T acute lymphoblastic leukemia (T-ALL)**, not for B ALL [1]. - B ALL does not involve T cell precursors; the focus is solely on **immature B cells** [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 596-600.
Question 3: In the context of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML), which of the following cytogenetic abnormalities is associated with the worst prognosis?
- A. inv(16)
- B. Normal cytogenetics
- C. Monosomy 7 (Correct Answer)
- D. t(8;21) translocation
Explanation: ***Monosomy 7*** - Monosomy 7 is associated with **poor prognosis** in conditions like **acute myeloid leukemia (AML)**, often leading to a higher risk of treatment failure. - It implies more aggressive disease and often correlates with **poor response to therapy**. *8/21 translocation* - Generally indicates a more favorable prognosis [1], commonly seen in **Acute Lymphoblastic Leukemia (ALL)**. - Associated with **treatment responsiveness** and a higher chance of remission compared to other cytogenetic abnormalities. *Normal cytogenetics* - In many leukemias, **normal cytogenetics** suggest a relatively **better prognosis** [1] and a more favorable response to treatment. - It is often an indicator of **favorable disease characteristics** and lower risk of relapse. *Inversion 16* - Typically associated with **acute myeloid leukemia (AML)** and indicates a **better prognosis** [1] due to a favorable response to therapy. - Patients with this cytogenetic change generally exhibit **good overall outcomes** compared to other abnormalities. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 620.
Question 4: Specific stain for myeloblasts is
- A. Sudan black B
- B. Periodic acid-Schiff (PAS)
- C. Leukocyte alkaline phosphatase (LAP)
- D. Myeloperoxidase (Correct Answer)
Explanation: ***Myeloperoxidase*** - **Myeloperoxidase (MPO)** is an enzyme found in the primary granules of myeloblasts and other myeloid cells, making it a specific marker. - A positive MPO stain helps differentiate **acute myeloid leukemia (AML)** from **acute lymphoblastic leukemia (ALL)**. *Sudan black B* - **Sudan black B (SBB)** stains lipids within granules of myeloid and monocytoid cells, including myeloblasts. - While it is positive in myeloblasts, it is **less specific** than MPO as it can also stain monocytes, and its staining mechanism is different from enzyme activity. *Periodic acid-Schiff (PAS)* - **PAS stain** detects glycogen and other carbohydrates, typically showing a granular pattern in ALL and often negative or weakly positive in AML. - It is **not specific for myeloblasts** and is more characteristic of erythroblasts and lymphoblasts. *Leukocyte alkaline phosphatase (LAP)* - **LAP score** is used to distinguish between chronic myeloid leukemia (CML), which typically has a low LAP score, and other myeloproliferative disorders or leukemoid reactions, which have high scores. - It is **not used for the identification of myeloblasts** or for distinguishing AML from ALL.
Question 5: Which of the following is used to detect abnormal gene sequences EXCEPT?
- A. RFLP analysis
- B. Pyrosequencing
- C. Flow cytometry (Correct Answer)
- D. FISH
Explanation: ***Flow cytometry*** - **Flow cytometry** is primarily used to analyze **cell populations** based on their physical and biochemical characteristics (e.g., size, granularity, and protein expression) by passing them single file through a laser beam, not for direct gene sequencing. - It detects and quantifies cells labeled with **fluorescent antibodies**, making it useful for immunophenotyping, cell sorting, and DNA content analysis, but not for identifying specific gene sequences or mutations. *RFLP analysis* - **Restriction fragment length polymorphism (RFLP) analysis** detects variations in **DNA sequences** by using **restriction enzymes** to cut DNA at specific sites. - Differences in fragment lengths indicate **polymorphisms** or **mutations** within the recognition sites, thereby identifying abnormal gene sequences. *Pyrosequencing* - **Pyrosequencing** is a method of **DNA sequencing** that determines the sequence of nucleotides by detecting the release of pyrophosphate during DNA synthesis. - It is used to identify **single nucleotide polymorphisms (SNPs)** and **short genetic variations**, making it suitable for detecting abnormal gene sequences. *FISH* - **Fluorescence in situ hybridization (FISH)** uses **fluorescently labeled DNA probes** that bind to specific complementary **DNA sequences** on chromosomes. - It is a powerful cytogenetic technique for detecting **chromosomal abnormalities**, such as deletions, translocations, and amplifications, thereby identifying abnormal gene sequences.
Question 6: Among the following AML subtypes, non-specific esterase (NSE) staining is typically NEGATIVE in which one?
- A. Acute Erythroleukemia (M6)
- B. Acute Promyelocytic Leukemia (M3) (Correct Answer)
- C. Acute Myelomonocytic Leukemia (M4)
- D. Acute Monocytic Leukemia (M5)
Explanation: ***Acute Promyelocytic Leukemia (M3)*** - Non-specific esterase (NSE) is **negative** in Acute Promyelocytic Leukemia (M3) because NSE primarily stains cells of the **monocytic lineage**. - M3 is characterized by abnormal **promyelocytes** with heavy granulation, which are granulocytic precursors without monocytic differentiation. - M3 shows strong positivity for **myeloperoxidase (MPO)** instead, which is the characteristic marker for granulocytic lineage. *Acute Myelomonocytic Leukemia (M4)* - NSE staining is **positive** in M4 because this subtype has both myeloid and **monocytic components**. - The monocytic component (≥20% of non-erythroid cells) stains positively with NSE, which helps differentiate it from pure myeloid leukemias. - NSE positivity (inhibited by sodium fluoride) is a key diagnostic feature alongside myeloperoxidase positivity. *Acute Erythroleukemia (M6)* - NSE is typically **negative** in the predominant erythroid component of M6. - The diagnosis of M6 relies on the presence of ≥50% erythroid precursors (which are PAS positive) and ≥20% myeloblasts among non-erythroid cells. - NSE is not a characteristic marker for erythroleukemia. *Acute Monocytic Leukemia (M5)* - NSE staining is characteristically **strongly positive** in M5, which primarily consists of **monoblasts and promonocytes**. - This strong NSE positivity (inhibited by sodium fluoride) is a defining diagnostic feature demonstrating pure monocytic differentiation. - M5 typically shows weak or negative myeloperoxidase, helping distinguish it from other AML subtypes.
Question 7: What is the most common type of acute myeloid leukemia in patients with Down's syndrome?
- A. Acute megakaryoblastic leukemia M7 (Correct Answer)
- B. Acute myeloid leukemia M1
- C. Acute promyelocytic leukemia M3
- D. Acute myeloid leukemia M2
Explanation: ***Acute megakaryoblastic leukemia M7*** - **Acute megakaryoblastic leukemia (AML M7)** is significantly more common in children with **Down's syndrome (trisomy 21)**, particularly those under 5 years of age. - This association is thought to be due to an increased copy number of certain genes on **chromosome 21** that are involved in hematopoiesis and leukemogenesis. [3] *Acute myeloid leukemia M1* - This subtype, characterized by proliferation of **myeloblasts without maturation**, is not specifically associated with Down's syndrome. [1] - It is a more undifferentiated form of AML. *Acute promyelocytic leukemia M3* - Characterized by the t(15;17) translocation involving the **PML-RARα fusion gene**, resulting in a block in myeloid differentiation at the promyelocyte stage. [2], [4], [5] - This subtype is associated with a specific genetic abnormality and is not preferentially seen in patients with Down's syndrome. *Acute myeloid leukemia M2* - This subtype involves **myeloblasts with maturation** and a characteristic t(8;21) chromosomal translocation. [2] - While it's a common form of AML, it does not show the specific strong association with Down's syndrome that AML M7 does. **References:** [1] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 607-608. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 620. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Genetic Disorders, pp. 170-171. [4] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 621-622. [5] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 620-621.
Question 8: BCR-ABL fusion gene is MOST CHARACTERISTICALLY seen in?
- A. CML (Correct Answer)
- B. AML
- C. Chronic Lymphocytic Leukemia (CLL)
- D. Acute Lymphoblastic Leukemia (ALL)
Explanation: ***CML*** - The **BCR-ABL gene mutation** is characteristic of **Chronic Myeloid Leukemia (CML)**, resulting from a translocation between chromosomes 9 and 22 [1]. - This mutation leads to the production of the **BCR-ABL fusion protein**, which promotes cell proliferation and inhibits apoptosis [1]. *AML* - Acute Myeloid Leukemia (AML) does not typically exhibit the **BCR-ABL fusion gene**; rather, it is associated with various other genetic mutations. - Key features of AML include **myeloblast proliferation** and it presents with different cytogenetic abnormalities like **FLT3 or NPM1 mutations**. *CLL* - Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of **mature lymphocytes**, not the **BCR-ABL mutation**. - It is often associated with mutations such as **TP53** and **NOTCH1**, distinct from myeloid malignancies. *ALL* - Acute Lymphoblastic Leukemia (ALL) is primarily linked with **chromosomal translocations** involving **the TCF3** gene or others, but not specifically with **BCR-ABL**. - In ALL, **lymphoid progenitor cells** proliferate, whereas CML is primarily a **myeloid process** associated with the BCR-ABL gene [1]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 624-625.
Question 9: A bone marrow aspirate shows blast cells with multiple Auer rods arranged in bundles ('faggot cells'). Which molecular finding would confirm acute promyelocytic leukemia?
- A. BCR-ABL translocation
- B. PML-RARA translocation (Correct Answer)
- C. AML1-ETO translocation
- D. inv(16) mutation
Explanation: PML-RARA translocation - The presence of **multiple Auer rods** in bundles, described as "faggot cells," is highly characteristic of **acute promyelocytic leukemia (APL)** [1], [2]. - APL is cytogenetically defined by the **t(15;17) translocation**, which fuses the **PML (promyelocytic leukemia) gene** on chromosome 15 with the **RARA (retinoic acid receptor alpha) gene** on chromosome 17 [1], [2], [3]. *BCR-ABL translocation* - This translocation, **t(9;22)**, creates the **Philadelphia chromosome** and is the hallmark of **chronic myeloid leukemia (CML)** [3]. - While it can be seen in some acute leukemias, it does not typically present with the characteristic **Auer rods** or "faggot cells" associated with APL. *AML1-ETO translocation* - This refers to the **t(8;21)** chromosomal translocation, a common cytogenetic abnormality found in **acute myeloid leukemia (AML) with maturation**, specifically AML M2 [2]. - While AML1-ETO AML can have Auer rods, it does not typically present with the bundles ("faggot cells") seen in APL [2]. *inv(16) mutation* - The **inv(16) inversion** is associated with **acute myelomonocytic leukemia with eosinophilia (AML M4Eo)** [2]. - This subtype of AML is characterized by **abnormal eosinophils** and can have Auer rods, but it does not present with the specific "faggot cell" morphology that points to APL [2]. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 620-622. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, p. 620. [3] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Blood And Bone Marrow Disease, pp. 605-607.
Question 10: Myeloid sarcoma, which is a tumor mass consisting of myeloid blasts occurring at anatomic sites other than the bone marrow, is often characterized by chromosome aberrations. Which of the following is NOT typically associated with myeloid sarcoma?
- A. Monosomy 7
- B. t (15;17) (Correct Answer)
- C. Trisomy 8
- D. inv (16)
Explanation: ***t (15;17)*** - The **t(15;17) translocation** is pathognomonic for **acute promyelocytic leukemia (APL, AML-M3)**, a specific subtype of AML characterized by abnormal promyelocytes [1]. - **APL rarely presents with extramedullary involvement** or myeloid sarcoma. The leukemic cells in APL typically remain confined to the bone marrow and peripheral blood [2]. - This makes t(15;17) the chromosomal abnormality **NOT typically associated** with myeloid sarcoma, unlike the other options listed [1]. *Monosomy 7* - **Monosomy 7** is a recurrent chromosomal abnormality associated with a poor prognosis in myeloid malignancies, including various forms of **acute myeloid leukemia (AML)** and **myeloid sarcoma**. - It indicates a loss of an entire chromosome 7, often linked to **myelodysplastic syndromes (MDS)** and therapy-related AML, both of which can present with myeloid sarcoma. *Trisomy 8* - **Trisomy 8** is one of the most common cytogenetic abnormalities found in **AML** and is **frequently observed in cases of myeloid sarcoma**. - It involves an extra copy of chromosome 8 and is associated with an intermediate prognosis. - Myeloid sarcomas with trisomy 8 can occur at various anatomic sites. *inv (16)* - **Inv(16)(p13q22)** is a specific chromosomal inversion associated with **acute myeloid leukemia (AML)** with **myelomonocytic differentiation** and **abnormal eosinophils** [1]. - This inversion leads to the formation of the **CBFB-MYH11 fusion gene**, and AML with inv(16) **can present as myeloid sarcoma**, particularly in soft tissues [1]. - This is a recognized chromosomal abnormality in myeloid sarcoma cases. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 620-621. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus, pp. 621-622.
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