BCR-ABL1 positive AML or CML in blast crisis? A pediatric case report with inv(3) and t(9;22) in the initial clone

Abstract

The co-occurrence of an inversion inv(3)(q21q26)/ GATA2-MECOM and a Philadelphia translocation t(9;22)(q34;q11)/ BCR-ABL1 in the context of chronic myeloid leukemia (CML) in blast crisis or acute myeloid leukemia (AML) has only rarely been described. To our knowledge, this co-occurrence has been reported in six pediatric patients with CML but not in pediatric patients with AML.Here, we report on a 7-year-old girl, who, presented with a t(9;22) and inv(3) in 14 of 15 metaphases and an additional monosomy 7 was detected in 5 of these metaphases (ISCN: 46, XX, inv(3)(q21q26), t(9;22)(q34q11)[9]/45, idem, -7[5]/46, XX[1]). The p190 BCR-ABL1 fusion transcript was detected by multiplex PCR and targeted RNA sequencing. Due to these results, a clear distinction between a CML in blast crisis and a BCR-ABL1 positive AML was not possible. The patient was treated according to the treatment recommendations of the AML-BFM study group and additionally received tyrosine kinase inhibitor therapy (Dasatinib). The treatment with Dasatinib was successful in eliminating the inv(3)/t(9;22) clone, but the ancestral inv(3) clone persisted. Based upon these findings we diagnosed an AML with inv(3) and a secondary acquisition of t(9;22). This treatment as well as an allogenic transplantation has led to a complete remission of the disease up to this date (21 months post diagnosis).

Inv(3) Acute Myeloid Leukemia in a Young Adult and Review of the Literature

“…This variant is more commonly seen in adults and is exceedingly rare in pediatric patients [1,3,4]. Within the literature, only four cases of inv(3) AML have been reported in patients aged 0-18 years (Table 1) [11][12][13][14]. While the specific treatment and clinical course data are not available for the published cases, the treatment refractory nature of the inv(3) variant was highlighted.…”

“…With the use of next-generation sequencing (NGS), additional mutations in RAS/RTK signaling pathways have also been detected alongside inv(3), indicating the possible application of FLT3 or PIK3 inhibition in these patients [4,9]. One case showed achievement of CR in an adult patient with inv(3) AML following treatment with dasatinib, a tyrosine kinase inhibitor targeting AKT/STAT3, allowing for successful HSCT [14]. Hypomethylating agents (HMAs) such as azacitidine or decitabine have been used for many years in the treatment of AML, including the pediatric population [16,17].…”

Management of children and adolescents with chronic myeloid leukemia in blast phase: International pediatric CML expert panel recommendations

“…If de novo CML-BP presents as an acute myeloid neoplasm, an assignment based on cytogenetics or molecular genetics by detection of the t(9;22) translocation or the BCR::ABL1 fusion transcript becomes obvious, because acute myeloid leukemia (AML) with BCR::ABL1 is a rare entity. In the AML-BFM trials, only six children with Ph + AML were diagnosed among a total cohort of nearly 1500 patients with AML (age range: 1-18 years) over a period of 16 years (Dirk Reinhardt, AML-BFM study chair, database query January 1, 2022), and it is unclear if single cases could not also have been designated as myeloid BP [20]. However, in 2016, the World Health Organization added AML harboring BCR::ABL1 as a new category of AML that might benefit from TKI therapy [21].…”