Chromosomal Abnormality Associated with Bone Marrow Eosinophilia in Acute Myelomonocytic Leukemia
The chromosomal abnormality inv(16) (option E) is associated with an increase in bone marrow eosinophils in acute myelomonocytic leukemia.
Explanation of the Association
Inv(16)(p13.1q22) represents a pericentric inversion of chromosome 16 that is strongly associated with a specific subtype of acute myeloid leukemia (AML) - acute myelomonocytic leukemia with abnormal bone marrow eosinophilia, classified as AML-M4Eo in the French-American-British (FAB) classification system.
Molecular Basis
- The inv(16) abnormality results in the fusion of two genes:
- CBFB (Core Binding Factor Beta) on 16q22
- MYH11 (Myosin Heavy Chain 11) on 16p13.1
- This creates a CBFB-MYH11 fusion gene that disrupts normal myeloid differentiation 1
- The presence of this fusion transcript is closely associated with abnormal bone marrow eosinophils in AML-M4Eo 1
Evidence Supporting This Association
- Multiple studies have confirmed that CBFB-MYH11 transcripts are present in most cases of inv(16) AML and are specifically associated with bone marrow eosinophilia 1, 2
- According to the WHO classification, the presence of inv(16)(p13.1q22) or t(16;16)(p13.1;q22) with CBFB-MYH11 fusion is sufficient for the diagnosis of AML regardless of blast percentage 3
- The 2017 European LeukemiaNet (ELN) guidelines classify inv(16)(p13.1q22) or t(16;16)(p13.1;q22) with CBFB-MYH11 fusion as a favorable risk genetic abnormality 3
Distinguishing from Other Chromosomal Abnormalities
t(8;21) (Option B)
- Associated with AML-M2 (acute myeloblastic leukemia with maturation)
- Results in RUNX1-RUNX1T1 fusion
- Does not typically present with bone marrow eosinophilia
- Also considered favorable risk 3
t(9;22) (Option C)
- Known as the Philadelphia chromosome
- More commonly associated with chronic myeloid leukemia (CML) and some cases of acute lymphoblastic leukemia (ALL)
- Not specifically associated with bone marrow eosinophilia in AML
- Considered adverse risk in AML 3
t(15;17) (Option D)
- Characteristic of acute promyelocytic leukemia (APL or AML-M3)
- Results in PML-RARA fusion
- Associated with hypergranular promyelocytes, not eosinophilia
- Considered favorable risk with specific ATRA/arsenic trioxide therapy 3
+8 (Option A)
- Trisomy 8 is a common numerical abnormality in AML
- Not specifically associated with bone marrow eosinophilia
- Generally considered intermediate risk 3
Clinical Significance
The identification of inv(16) in acute myelomonocytic leukemia has important prognostic implications:
- Patients with inv(16) have a favorable prognosis compared to standard-risk AML 3
- This abnormality is classified in the favorable risk category in both pediatric and adult AML risk stratification systems 3
- The CBFB-MYH11 fusion transcript can be used as a marker for minimal residual disease monitoring during treatment 1
In summary, among the chromosomal abnormalities listed, inv(16) (option E) is uniquely associated with increased bone marrow eosinophils in acute myelomonocytic leukemia, representing a distinct clinicopathologic entity with favorable prognosis.