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Updated: May 21, 2026
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Molecular characterization of de novo Philadelphia chromosome-positive acute myeloid leukemia
Sergej Konoplev1, C Cameron Yin, Steven M Kornblau
1Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. skonople@mdanderson.org
Abstract:
Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) is a controversial diagnosis, as others propose that it represents chronic myelogenous leukemia in blast phase (CML-BP). NPM1 mutations occur in 25-35% of patients with AML but are absent in patients with CML. Conversely, ABL1 mutations occur in 25% of imatinib-naive patients with CML-BP but are not described in patients with AML. We analyzed for NPM1 and ABL1 mutations in nine Ph+ patients with AML and five patients with CML-BP initially presenting in BP. In six cases of Ph+ AML, we screened for a panel of gene mutations using Sequenome(®)-based methods including AKT1, AKT2, AKT3, BRAF, EGFR, GNAQ, GNAS, IDH1, IDH2, KRAS, MET, NRAS, PIK3CA and RET. Two of nine (22%) patients with Ph+ AML had NPM1 mutations and were alive 36 and 71 months after diagnosis. All cases of Ph+ AML were negative for ABL1 and other gene mutations. One (20%) patient with CML-BP had ABL1 mutation; no patients had NPM1 mutations. These data suggest that Ph+ AML is distinct from CML-BP.
Insights
Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) is distinct from chronic myelogenous leukemia in blast phase (CML-BP). Ph+ AML patients lack ABL1 mutations, unlike CML-BP, and some harbor NPM1 mutations, which are absent in CML-BP.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Philadelphia chromosome-positive acute myeloid leukemia (Ph+ AML) diagnosis is debated, with some classifying it as chronic myelogenous leukemia in blast phase (CML-BP).
- NPM1 mutations are common in AML but absent in CML, while ABL1 mutations are found in CML-BP but not AML.
Purpose of the Study:
- To investigate the molecular differences between Ph+ AML and CML-BP.
- To determine the presence of NPM1 and ABL1 mutations in Ph+ AML and CML-BP cohorts.
Main Methods:
- Analysis of NPM1 and ABL1 mutations in nine Ph+ AML patients and five CML-BP patients.
- Screening for additional gene mutations (AKT1, BRAF, EGFR, etc.) in Ph+ AML cases using Sequenome-based methods.
Main Results:
- Two of nine (22%) Ph+ AML patients had NPM1 mutations; all Ph+ AML cases were negative for ABL1 and other tested mutations.
- One of five (20%) CML-BP patients had an ABL1 mutation; no CML-BP patients had NPM1 mutations.
Conclusions:
- The distinct mutation profiles suggest Ph+ AML is a separate entity from CML-BP.
- NPM1 mutations may serve as a distinguishing marker for Ph+ AML.
