Does BCR/ABL1 positive acute myeloid leukaemia exist?

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• The BCR/ABL1 fusion gene, often on the Philadelphia chromosome (Ph), defines chronic myeloid leukemia (CML) but also occurs in acute leukemias.
• While common in acute lymphoblastic leukemia (ALL), its presence in de novo acute myeloid leukemia (AML) is rare, necessitating clear diagnostic markers.

Purpose of the Study:

• To investigate the genomic profiles of Philadelphia chromosome-positive AML (Ph+ AML) and compare them with Ph+ ALL.
• To identify specific genomic aberrations that differentiate de novo Ph+ AML from other BCR/ABL1-positive leukemias, particularly CML in myeloid blast crisis.

Main Methods:

• Array Comparative Genomic Hybridization (aCGH) was employed to analyze genomic alterations in six Ph+ AML, three bi-lineage, and four Ph+ ALL samples.
• Significance Analysis of Microarrays (SAM) was applied to identify differentiating genomic features between Ph+ AML and other BCR/ABL1-positive leukemia subtypes.

Main Results:

• Recurrent losses of IKZF1 and CDKN2A, typical of Ph+ ALL, were also observed in Ph+ AML.
• Cryptic deletions within immunoglobulin and T cell receptor genes were found in Ph+ AML, similar to those in Ph+ ALL and CML.
• Distinct genomic aberrations unique to de novo Ph+ AML were identified, differentiating them from CML blast crisis.

Conclusions:

• Ph+ AML exhibits genomic similarities to Ph+ ALL, including IKZF1 and CDKN2A deletions.
• Specific genomic losses, particularly within immunoglobulin genes, can distinguish de novo Ph+ AML from the myeloid blast crisis of CML.
• Further research is needed to elucidate the biological and clinical implications of the unique genomic signature found in Ph+ AML.