Rare Leukaemia Case Reveals Aggressive Blood Cancer Wearing Two Masks at Once

In the world of blood cancers, few diagnoses are as elusive as acute basophilic leukaemia, an ultra-rare form of acute myeloid leukaemia in which the malignant cells commit to becoming basophils, the granulocytes best known for releasing histamine in allergic reactions. Even rarer is the scenario now documented by haematologists at Peking University International Hospital: a patient whose disease met the criteria for two aggressive WHO-defined entities at the same moment. In a case report published in Holistic Integrative Oncology, Jian-xin Liu and colleagues describe a 67-year-old man diagnosed simultaneously with acute myeloid leukaemia-myelodysplasia related (AML-MR) and acute basophilic leukaemia (ABL), a combination the authors believe has never been reported before at initial diagnosis.

The case began deceptively. The patient, previously healthy, arrived at the hospital in November 2019 with a one-month history of cough. He had no exposure history to toxins, dust or radiation, no family history of haematological disease, and, strikingly, no physical signs that would raise immediate alarm: no enlarged spleen or liver, no swollen lymph nodes, no skin involvement, and none of the flushing, itching or other symptoms of hyperhistaminemia that often accompany basophil-driven leukaemias. Yet his blood counts told a grimmer story. He was profoundly pancytopenic, with a white cell count of just 2.41 × 10⁹ per litre, haemoglobin of 3.7 g/dL and platelets of 12 × 10⁹ per litre, and a differential count in which a remarkable 60 percent of his circulating white cells were basophils.

A bone marrow aspirate deepened the puzzle. The marrow was hypocellular, containing 25 percent blast cells alongside 28 percent immature basophils. The blasts were medium-sized, with immature nuclei and moderate cytoplasm studded with coarse basophilic granules; no Auer rods were seen, and there was no morphological evidence of dysplasia or haemophagocytosis. When stained with toluidine blue, the blasts and immature basophils displayed metachromasia, the colour-shift reaction that is the cytological hallmark of the basophil and mast cell lineages. Electron microscopy went further, confirming round cytoplasmic granules packed with finely particulate electron-dense material inside the leukaemic cells.

Immunophenotyping by flow cytometry revealed two distinct malignant populations. The blasts expressed the stem cell and myeloid markers CD34, CD33, CD13, CD45, HLA-DR and CD117, while the immature basophils carried the basophil-associated signature CD33, CD13, CD203c, CD123, CD9, CD22, CD15 and CD11b. Critically, neither population expressed myeloperoxidase, a cytochemical negativity that is central to distinguishing basophilic leukaemia from other myeloid proliferations and, in the 2022 WHO framework, from mast cell leukaemia. Serum tryptase and histamine were normal, arguing against a mast cell disorder and helping to lock in the diagnosis of acute basophilic leukaemia.

The genetics, however, shifted the classification decisively. Conventional cytogenetics uncovered a complex karyotype and monosomal karyotype, including a der(X;1)(p11;p22), monosomy 1, t(4;20)(q31;q11), a der(7;13)(p10;q10), trisomy 8, and multiple additional structural abnormalities. Reverse transcriptase PCR was positive for WT1 and PRAME and negative for PML-RARA, DEK-NUP214 and BCR-ABL1 fusions, excluding promyelocytic and chronic myeloid leukaemia-related entities. Next-generation sequencing of a 235-gene haematological malignancy panel identified a TP53 mutation (p.I255N) with a variant allele frequency of nearly 72 percent. Under the 2022 WHO classification, these MDS-defining cytogenetic abnormalities override morphological categories, meaning the patient’s disease was formally classified as AML-MR presenting with acute basophilic leukaemia, and placed firmly in the high-risk category.

AML-MR itself is a category that has evolved considerably since its introduction in the 2008 WHO classification. It defines a clonal myeloid neoplasm with 20 percent or more blasts carrying the cytogenetic or molecular abnormalities typically seen in myelodysplastic syndromes, whether arising de novo or after known MDS or MDS/MPN. Its prognosis is among the poorest in acute myeloid leukaemia, driven largely by age, antecedent disease and karyotype. Retrospective analyses have shown that patients with MDS-defining cytogenetic abnormalities have markedly shortened overall survival, with median survival of roughly 4 to 7 months when complex or monosomal karyotypes are present, and that multiple TP53 mutations predict even worse outcomes than a single mutant allele.

Acute basophilic leukaemia, meanwhile, accounts for less than 2 percent of all haematopoietic malignancies, and most reported cases have emerged as transformation from chronic myeloid leukaemia, myelodysplastic syndromes or myeloproliferative neoplasms rather than as a de novo diagnosis. Its reported survival ranges from 2 to 16 months, reflecting a rapid clinical course and frequent resistance to therapy. Diagnostic consensus requires metachromasia on toluidine blue staining, negativity for myeloperoxidase, Sudan black B and non-specific esterase, and the absence of strong CD117 expression to exclude mast cell leukaemia, all features satisfied in this case. No characteristic marker chromosome has been described for ABL, underscoring how much remains unknown about its biology.

Treatment presented a dilemma familiar to oncologists treating elderly, high-risk patients. Because of the patient’s high ECOG performance status concerns, the team chose decitabine combined with a lower-dose CAG regimen, cytarabine, aclarubicin and G-CSF priming, a hypomethylating agent-based strategy known as D-CAG. The disease responded completely. After four consolidation courses, the patient remained in remission for ten months, a notable achievement given his constellation of adverse factors. Intriguingly, when he relapsed in September 2020, the leukaemia had shed its basophilic identity: abundant blasts were present, but no basophils were detectable by morphology or flow cytometry, while the complex karyotype and the TP53 p.I255N mutation persisted at a slightly higher variant allele frequency. The authors suggest that the hypomethylating agent may have been responsible for the unusually durable first remission, noting literature indicating that epigenetic drugs such as hypomethylating agents and histone deacetylase inhibitors can be effective against TP53-mutated AML.

The relapse proved merciless. The patient’s disease resisted multiple successive therapies, including venetoclax, dasatinib, arsenite and homoharringtonine, and he died of sepsis in February 2021. Allogeneic haematopoietic stem cell transplantation, which offers a modest survival benefit in TP53-mutated complex-karyotype AML, was declined because of age and economic constraints. The case thus illustrates both the promise and the limits of current approaches: epigenetic combination therapy can buy meaningful time even in molecularly ominous disease, but relapsed TP53-mutant AML remains one of haemato-oncology’s most stubborn challenges.

The report arrives amid a wave of investigational strategies aimed squarely at TP53-mutant myeloid neoplasms. Eprenetapopt, a first-in-class reactivator of mutant p53, combined with azacitidine produced an overall response rate of 71 percent and a median overall survival of 10.8 months in TP53-mutant MDS and AML, while the anti-CD47 antibody magrolimab plus azacitidine achieved an overall response rate of 71 percent and a median overall survival of 12.9 months in an early-phase trial. Immune checkpoint inhibitors, CD123 × CD3 bispecific antibodies and CAR-T cell therapies are all under study, though none has yet delivered breakthrough efficacy in this genetically defined subgroup. For clinicians, the message of this singular case is twofold: basophilic differentiation can be the presenting face of AML-MR, and cytogenetics must trump morphology when the two diverge; and for the growing population of patients with TP53-mutated, complex-karyotype disease, the therapeutic frontier lies in targeted and immunological approaches that do not yet exist in standard practice. As the first documented instance of AML-MR presenting as acute basophilic leukaemia at diagnosis, the case adds a rare but instructive data point to the literature on two of the most feared entities in myeloid malignancy.

Subject of Research: A rare case of acute myeloid leukaemia-myelodysplasia related presenting as acute basophilic leukaemia at diagnosis.

Article Title: Acute myeloid leukaemia-myelodysplasia related (AML-MR) presented with acute basophilic leukaemia at diagnosis

Article References: Liu, J.-X., Wang, C.-J., & Zhang, M.-X. (2026). Acute myeloid leukaemia-myelodysplasia related (AML-MR) presented with acute basophilic leukaemia at diagnosis. Holistic Integrative Oncology, 5(1), Article 68. https://doi.org/10.1007/s44178-026-00291-8

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00291-8

Keywords: acute myeloid leukaemia, AML-MR, acute basophilic leukaemia, myelodysplasia, TP53 mutation, complex karyotype, decitabine, hypomethylating agents, WHO classification, flow cytometry, leukaemia relapse, targeted therapy