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Cup‑like blasts in acute myeloid leukemia (AML) were first described by Kussick et al. in 2004 [1], who identified 19 patients exhibiting deep nuclear invaginations characteristic of “cup‑like” morphology. These cases were frequently HLA-DR-negative and FLT3‑ITD‑positive, suggesting a biologically distinct subset of AML. In 2008, Kroschinsky et al. expanded this concept by reporting 55 additional cases associated with FLT3 and/or NPM1 mutations and typically a normal karyotype [2]. Clinically, cup-like AML often presents with high white blood cell counts, elevated blast percentages, and low expression of CD34 and HLA‑DR [2]. Further studies demonstrated that cup‑like nuclear morphology is not restricted to a single AML subtype; rather, it appears in up to 21% of all AML cases [2, 3], across all FAB classifications [3], including AML M3 [4], and even in acute lymphoblastic leukemia [5] and BCR‑ABL‑positive AML [6]. Thus, cup‑like morphology represents a common but non‑specific finding across diverse leukemic entities. Despite its morphological heterogeneity, typical cup‑like AML is often categorized as FAB AML M1 or shows monocytic features, and cytogenetically, it frequently exhibits a normal karyotype [4]. In terms of clinical management, tumor lysis syndrome (TLS) is a recognized risk factor for highly proliferative leukemias, such as cup‑like AML. Cup-like leukemia may be particularly susceptible due to rapid proliferation and a high leukocyte burden [2]. However, no prior study has directly evaluated whether cup‑like AML carries a higher risk of acute kidney injury (AKI) than non‑cup‑like AML as a consequence of TLS. We encountered a representative case (70-yearsold female) of cup‑like AML classified as FAB AML M1, harboring an FLT3‑ITD mutation, expressing CD34, and lacking HLA‑DR. At presentation, the patient had a white blood cell count of 159,630/µL with 91.6% blasts. Bone marrow blasts showed limited nuclear invagination (Figure 1a), whereas peripheral blood blasts displayed the characteristic cup‑like morphology (Figure 1b). Induction chemotherapy with idarubicin and cytarabine produced an initial therapeutic response; however, the patient developed a dramatic rise in serum phosphate from 2.8 mg/dL at baseline to 13.1 mg/dL by Day 8. This severe hyperphosphatemia persisted for one week and led to AKI, with serum creatinine increasing to 4.78 mg/dL. We attributed the AKI to sustained hyperphosphatemia. Continuous hemodiafiltration (CHDF) was initiated on Day 8, resulting in renal recovery by Day 15. Unfortunately, the patient subsequently developed intracranial hemorrhage, secondary to disseminated intravascular coagulation (DIC), and ultimately died on Day 26 due to leukemic regrowth. Electron microscopy studies have shown that cup‑like nuclear invaginations often contain clusters of mitochondria [7, 8]. Because mitochondria are major reservoirs of phosphate, owing to their central role in oxidative phosphorylation and ATP synthesis [9], lysis of these cells can release large quantities of phosphate into circulation. Mitochondria store phosphate in the form of insoluble granules [9], and their disruption during chemotherapy‑induced tumor lysis can precipitate profound hyperphosphatemia [10, 11]. In TLS, massive phosphate release leads to calcium‑phosphate precipitation, which, together with uric acid crystals, obstructs renal tubules and triggers AKI [11, 12]. Hyperphosphatemia accompanied by hypercalcemia may further accelerate calcium‑phosphate deposition, increasing the risk of tissue calcification [10]. This mechanism may be particularly pronounced in cup-like AML, where mitochondrial accumulation within nuclear pockets could increase the phosphate burden released during cell death. Given this pathophysiology, careful monitoring of phosphate levels during induction therapy is essential. We recommend early and swift initiation of renal replacement therapy (RRT), including CHDF, when serum phosphate exceeds 10 mg/dL or when the calcium (mg/dL)–phosphate (mg/dL) product index (non‑dimension) surpasses 60. These thresholds align with established indications for emergent RRT in TLS, which include refractory hyperphosphatemia, hyperkalemia, hyperuricemia, hypocalcemia, volume overload, uncontrolled hypertension, severe acidosis, or uremia with neurological manifestations [10, 13]. Cup‑like AML has also been associated with coagulopathy, particularly DIC. Jost et al. reported a link between cup‑like morphology and dysregulated coagulation [8], although whether the morphology itself is an independent risk factor remains unclear. Strasser et al. noted that AML cases prone to DIC often exhibit cup‑like morphology or monocytic differentiation, excluding acute promyelocytic leukemia (APL) [14]. They further identified shared features among DIC‑prone non‑APL AML: CD34 and HLA‑DR negativity, and mutations in FLT3 and/or NPM1 [14]. Additional studies have shown that normal‑karyotype AML with NPM1 and/or FLT3‑ITD mutations is independently associated with DIC, characterized by prolonged PT and elevated D‑dimer levels [15]. These coagulopathic characteristics substantially overlap with the molecular and immunophenotypic profile of cup‑like AML. Behind the TLS mechanism, multiple cell‑death pathways may contribute to the clinical complications observed in acute leukemia. While apoptosis and necroptosis are foremost well‑recognized mechanisms of leukemic cell death during chemotherapy [16], other regulated forms, such as pyroptosis and NETosis, have been increasingly recognized in the Nomenclature Committee on Cell Death (NCCD). NETosis, in particular, promotes thrombosis and systemic inflammation, potentially exacerbating DIC. Moreover, AML cells with FLT3‑ITD mutations often express high levels of receptor‑interacting serine/threonine‑protein kinases 1 (RIPK1), a kinase involved in necroptotic signaling, which may enhance cell‑death‑associated phosphate release from mitochondria [16]. Taken together, these mechanisms suggest that cup‑like AML may be predisposed to a cascade of TLS, hyperphosphatemia, AKI, and DIC, driven in part by the high phosphate content of cup‑like blasts. Clinical outcome studies have reported variable but often poor prognoses for cup‑like AML, likely reflecting the heterogeneity of this morphological category [17]. Nevertheless, cup‑like morphology is frequently regarded by clinicians as a warning sign for aggressive disease behavior, including coagulopathy and TLS‑related complications [18]. AKI, in particular, may significantly worsen outcomes and is often intertwined with hyperleukocytosis, rapid proliferation, DIC, and TLS. In conclusion, we present indirect but compelling evidence that cup‑like AML may carry an elevated risk of AKI due to severe hyperphosphatemia arising from phosphate‑rich blasts. Given the potential for rapid clinical deterioration, vigilant monitoring of phosphate levels and early initiation of RRT are essential components of management in these patients. O.I. and M.U. designed the research and analyzed data. O.I. wrote the paper. S.U. contributed to the intellectual review. A.T. performed research and analyzed data. M.U. managed the study. The authors have nothing to report. This work was supported by JSPS KAKENHI Grant Numbers 22K12842, 22K06768, and 23K11850. This research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The study protocol was approved by the institute's committee on human research. The patient has given their written informed consent to participate in the case study. The authors declare no conflicts of interest. The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.