A rare BCR-ABL1 transcript in Philadelphia-positive acute myeloid leukemia: case report and literature review

Abstract

BackgroundPhiladelphia (Ph) chromosome results from the reciprocal translocation t(9;22)(q34.1;q11.2) and is diagnostic for chronic myeloid leukemia (CML). However, this translocation is also found in acute lymphoid leukemia (ALL), as well as in rare cases of acute myeloid leukemias (AML). Most patients with CML harbor either the e13a2 or the e14a2 BCR-ABL fusion product, while a small subset of the cases expresses e1a2 or e19a2 transcripts. Moreover, several atypical BCR-ABL1 transcripts, beside the most common e1a2, e13a2 and e14a2, have been described, mainly in patients with CML. However, ALL and de novo AML may also carry BCR-ABL1 atypical transcripts which will confer a poor prognosis.Case presentationA 78-years old male was admitted at our hospital with clinical and laboratory features allowing to make the diagnosis of AML. No evidence of a preceding CML (splenomegaly or basophilia) was found. The karyotype on G-banded metaphases was 46,XY, t(9;22)(q34;q11). While the molecular analysis was ongoing, the patient started treatment based on hydroxyurea followed by 5-aza-2′-deoxycytidine. The molecular biology analysis revealed the simultaneous presence of the common p190 e1a2 and the rare e6a2 isoforms. Because of persistent pancytopenia and presence of blasts, according to the molecular data, he was then switched to tyrosine kinase inhibitors (TKIs) treatment. Nevertheless, after 2 months, the patient was still refractory to second line treatment dying because of a pulmonary infection.ConclusionThe atypical p190 e6a2 transcript seems to be associated in AML with aggressive disease. TKI therapy alone does not seem to control the disease. Prompt observations on these patients carrying rare BCR-ABL1 transcripts may help to establish optimal treatment approaches on these aggressive BCR-ABL1 phenotypes in different setting of patients.

Association of Chronic Myelogenous (Basophilic) Leukemia and the BCR/ABL Mutation in a Yucatan Barrow (Sus scrofa domestica)

“…As mentioned previously, the presence of the Philadelphia gene is a hallmark of CML and only a rare subset of acute myeloid leukemias (AML) (30,31). The barrow in this report appeared to display the standard stages of CML including a relatively insidious disease onset with a chronic phase in which symptoms waxed and waned followed by what might be considered a rapid or accelerated phase that progressed to a fatal blast crisis.…”

A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia–Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia

“…The effect of these drugs in the treatment of AML is unclear. However, several studies have suggested the potential of nilotinib as a therapeutic agent for AML that features BCR-ABL1 transcription ( 62 , 63 , 64 ). The potential of fostamatinib as a therapeutic agent in FLT3-ITD–positive AML has been supported by evidence of the importance of SYK in the regulation of FLT3 ( 59 ).…”

Advances in Fusion Gene Research and Fusion Gene Families in Hematological Malignancies

“…4,15 Even in the routine detection of FGs that are already well known, false negative results may occur because of variant fusion transcripts, such as BCR-ABL1 and their variant and rare isotypes. 17,18 Therefore, how to effectively identify rare and variant FGs poses great challenges for detection methods and data analysis.…”