Is acute myeloid leukemia a liquid tumor?

Abstract

Extramedullary manifestations of acute myeloid leukemia (AML) were described as early as the 19th century. However, the incidence, clinical significance, and pathobiology of extramedullary AML remain ill defined. We reviewed case reports, retrospective case series, pilot studies, and imaging studies of extramedullary leukemia (EML) to determine its frequency, characteristics, clinical presentation, and significance. EML precedes or accompanies development of AML and occurs during or following treatment, even during remission. Although imaging studies are rarely conducted and the true incidence of EML has yet to be verified, authors have reported several estimates based on retrospective and autopsy studies. The incidence of EML in patients with AML of all ages is estimated to be about 9% and EML in children with AML was detected in 40% of patients at diagnosis. The combination of positron emission tomography and computed tomography were the most sensitive and reliable techniques of detecting and monitoring EML. Based on our literature review, the frequency of EML is likely underreported. The well-documented nature of EML in AML patients suggests that AML can manifest as a solid tumor. The extent to which EML accompanies AML and whether EML is derived from bone marrow are unknown. Furthermore, questions remain regarding the role of the microenvironment, which may or may not facilitate the survival and proliferation of EML, and the implications of these interactions with regard to minimal residual disease, tumor cell quiescence, and relapse. Therefore, prospective studies of detection and characterization of EML in AML patients are warranted.

Isolated Mesenteric CD20-Positive Myeloid Sarcoma

“…In our case, the gastrointestinal (GI) symptoms justified investigation for a malignant neoplasm. While MS may occur at any site along the mesentery and GI tract, or at any point during the course of AML [3], it rarely causes GI symptoms. Only two cases of isolated non-mesenteric abdominal MS have been reported [4, 5], and isolated mesenteric MS occurring at initial diagnosis without BM involvement has been reported only once [2].…”

“…With only case reports and small retrospective studies available, the incidence of MS is unclear [2, 3]. We present an unusual, diagnostically-challenging case of isolated mesenteric MS without BM involvement [2, 3]. …”

Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia

“…S1A). In this model, approximately one-third of the mice normally develop extramedullary myeloid sarcoma consisting of leukemic cells, tumors that are infrequent in human AML patients (12). Treating mice with the anti-IL1RAP monoclonal antibody (mAb) 81.2 resulted in a significantly reduced frequency of leukemic cells in peripheral blood (PB) 35 d after transplantation, compared with the control group receiving an isotype control antibody (Fig.…”

Molecular and cellular aspects of extramedullary manifestations of acute myeloid leukemia

“…[11] Other genetic abnormalities diagnosed in EML patients include t(15:17), t(9:11), t(1:11), t(8:17), del(16q), del(5q), del(20q), monosomy 7, trisomy 4 and trisomy 8. [12] Moreover, according to the French-AmericanBritish classification, some AML types are associated with EML, including M4 and M5 monocytic leukemias and the M2 subtype. [13] The t(8:21) has been reported as the most common cytogenetic abnormality associated with EML, occurring both at presentation and upon relapse, and is associated with orbital involvement in infants.…”

“…Molecular abnormalities associated with EML have not been systematically defined; however, a well-documented molecular abnormality is a mutation in the nucleophosmin (NPM-1) gene. [12] Nucleolar phosphoprotein or NPM-1 is localized in nuclear foci and is a multifunctional protein expressed in various cells. [22] NPM-1 gene mutation is the most common molecular genetic abnormality in AML, particularly AML with normal karyotype.…”