Reduction of leukemia cell burden and restoration of normal hematopoiesis at 3 months of crizotinib treatment in RAN-binding protein 2 (RANBP2)–anaplastic lymphoma kinase (ALK) acute myeloid leukemia

Crizotinib treatment for refractory pediatric acute myeloid leukemia with RAN-binding protein 2-anaplastic lymphoma kinase fusion gene

“… 2 , 3 , 4 Myeloid neoplasms with ALK rearrangement are uncommon but several reports indicate that crizotinib is effective for these diseases. 5 , 6 The efficacy of an ALK inhibitor on leukemia cells with ALK rearrangement has been shown in vitro . 6 Furthermore, crizotinib reduced leukemia cells in acute myeloid leukemia (AML) with ALK rearrangement.…”

“… 6 Furthermore, crizotinib reduced leukemia cells in acute myeloid leukemia (AML) with ALK rearrangement. 5 …”

Crizotinib resistance in acute myeloid leukemia with inv(2)(p23q13)/RAN binding protein 2 (RANBP2) anaplastic lymphoma kinase (ALK) fusion and monosomy 7

“…The patient ages ranged from 3 to 75 years, and the disease was characterized by differentiation into monocytes and invariably associated with À7. We first treated the current patient with crizotinib, resulting in reduction of the leukemia cell burden and restoration of normal hematopoiesis, which reached the level of the conventional definition of the complete remission of AML (10). However, relapse occurred as early as on day 135 of crizotinib treatment, and the bone marrow was replaced almost entirely with ALK-mutated AML cells, presumably reflecting the instability or rapid proliferation rate of AML cells.…”

“…We described the course of the index patient in our previous reports (8,10). The woman, at the age of 75, presented with AML with features of myelodysplastic syndrome/myeloproliferative neoplasm.…”

“…Mononuclear cells prepared from the bone marrow aspirates at the first relapse before crizotinib treatment, containing more than 80% ALK-rearrangementepositive leukemia cells determined by interphase FISH analysis (10), and those at the second relapse after crizotinib were studied for the presence or absence of a mutation within the ALK-KD. Exons 20 to 25 of ALK and their flanking sequences were amplified by PCR from genomic DNA templates and subjected to direct sequencing of both strands (11,12).…”