67. An undiagnosed chronic myeloid leukemia (CML) with p190 BCR::ABL1 transcript, an extra Philadelphia chromosome, and IKARO

Chronic myeloid leukemia (CML) with p190 BCR::ABL1 transcript is rare but when present, it is usually associated with increased monocytes. IKZF1, a gene that encodes the lymphoid transcription factor IKAROS, is commonly deleted in B-lymphoblastic leukemia (B-ALL). Here, we describe a 66-year-old male with 2-weeks history of myalgias, night sweats, malaise, and fatigue, and white blood cells of 177K with 90% circulating blasts. At our institute, bone marrow examination showed ∼56% B-lymphoblasts, ∼3% myeloblasts, and increased monocytes (21%). Aberrant CD13 and CD25 expression was noted, which can be seen in B-ALL with BCR::ABL1 fusion (BAF). FISH leukemia panels detected 2-3 BAF, in 94.5% and 4% of the cells, consistent with an extra Ph+, and loss of IKZF1 locus in 91% of cells. RT-PCR showed BAF p190 breakpoint. The initial diagnosis was a B-ALL with BAF but given the presence of increased monocytes and left-shifted granulocytes, a preceding CML could not be ruled out. Subsequently, an abnormal karyotype with two clones was detected; one with an interstitial deletion of 7p leading to IKZF1 deletion, and t(9;22). Clone two, exhibited an extra Ph+, plus t(9;22); both clones were consistent with the proportion of abnormal cells detected by FISH 46,XY,del(7)(p15p11.2),t(9;22)(q34;q11.2)[19]/47,XY,t(9;22),+der(22)t(9;22)[1]. The immunophenotype obtained by flow cytometry/immunohistochemistry and RT-PCR was supportive of B-ALL. The morphologic picture along with the correlation of the karyotype, which detected two distinct cell populations, supported by FISH IKZF1/ BCR::ABL1 results led to a diagnosis of a preceding CML presenting in lymphoid blast crisis. Patient is undergoing initial