An asymptomatic 61‐year‐old man with BCR‐ABL‐positive bone marrow following autologous transplantation for multiple myeloma

Abstract

A 60-year-old male was referred with a recent diagnosis of multiple myeloma. He presented at an outside institution with severe low back pain due to pathologic compression fractures of the thoracic spine treated with T12 vertebroplasty and T11 kyphoplasty. Workup at our institution demonstrated an IgA kappa monoclonal protein (M-spike) of 1.83 g/dl. Bone marrow examination showed that 25% of the marrow cellularity consisted of plasma cells. Cytogenetic analysis was not performed. Blood studies showed: total calcium, 10.7 mg/dl; hemoglobin, 12.4 g/dl; hematocrit, 33.7%; albumin, 3.6 g/dl; and b2 microglobulin, 5.3 lg/ml. His 24-hour urine electrophoresis showed a total protein of 23.2 mg in 24 hours. The kappa free light chain was 69.7 mg/L, the lambda free light chain was 2.25 mg/L, and the kappa/lambda ratio was 31 (normal 0.26-1.65). Radiologic studies revealed diffuse osteopenia and lytic lesions in the humeri and the pelvic bones.

Detection of a rare BCR–ABL tyrosine kinase fusion protein in H929 multiple myeloma cells using immunoprecipitation (IP)-tandem mass spectrometry (MS/MS)

“…Until this report, only two reports of patient BCR-ABL fusions were detected using PCR amplification and gene sequencing; however, no molecular mechanistic data regarding expressed BCR-ABL protein was previously reported in MM (28,29). The literature supports the existence of a relationship between MM and CML as well as a relationship between MM and the myeloproliferative disorders (59,60).…”

“…Histopathology of H929 MM cells. Because the discovery of BCR-ABL fusion in H929 cells using our three IP-MS proteomics approach represents an unexpected event in MM (28,29), a FISH analysis with a dual-color BCR-ABL fusion probe against the Philadelphia chromosome t (9, 22)(q34;q11) was performed to detect the BCR-ABL translocation in H929 cells (Fig. 3C).…”

“…BCR-ABL is unexpected in MM because, unlike the leukemias and lymphomas, MM typically has no specific chromosomal abnormalities and is characterized by a genomic instability that involves both ploidy and structural translocation (27). There have only been two reports of MM patients with a Philadelphia chromosome t(9;22)(q34;q11), a 64-y-old woman presenting a P190 BCR-ABL hybrid transcript by PCR analysis (28) and a 61-y-old man showing BCR-ABL-positive bone marrow after autologous bone marrow transplantation (29).…”

Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis

“…7 We note that is very rare that multiple myeloma cells contain the BCR–ABL fusion, although it is common in chronic myeloid leukemia (CML). 8,9 Phosphorylation is one of the most important and most studied post-translational modifications (PTM) because it regulates signaling activity and important cellular functions including proliferation, growth, and survival, especially in diseases such as cancer. 1,10–12 Tandem mass spectrometry (MS/MS), in combination with enrichment steps such as immobilized metal affinity chromatography (IMAC) resin 13 or TiO 2 beads 14 as well as phosphotyrosine immunoprecipitation, 15 has been widely used to quantify and identify phosphorylation sites.…”

Reply to MacLeod et al.: Multiple myeloma plasma cells have chameleon characteristics

“…It is important to note that BCR-ABL fusions have been detected from MM patient plasma cells in bone marrow, so our findings represent a rare but not impossible occurrence (3,4). It is also known that some patients with MM have developed subsequent BCR-ABL-positive CML (5), and so a similar genetic situation may have occurred in our H929 cells.…”