Advances in AML Research
- Keith Posner
- Mar 10, 2025
- 5 min read
Latest advances in research into acute myeloid leukaemia
Acute myeloid leukemia (AML) is a malignancy characterized by the rapid proliferation of abnormal myeloid cells in the bone marrow, leading to impaired hematopoiesis. Recent research has led to significant advancements in understanding and treating AML, offering new hope for patients.
Before we start, here is information on my specific genetic disorder.
Smears non contributory. Await further studies.Trephine hypocellular with focal hypercellular areas, 20-25% CD34+ blasts.
The statement you provided seems to be related to the results of a bone marrow biopsy or aspirate report. Here's a breakdown of the key components:
Smears non-contributory: This suggests that the smears made from the sample were not useful or did not provide meaningful information, so further tests are needed.
Await further studies: Indicates that additional tests or analysis are needed to clarify the findings.
Trephine hypocellular with focal hypercellular areas: A trephine biopsy sample (a core sample of bone marrow) is "hypocellular," meaning there is a reduced number of cells overall, but there are areas where the cellularity is increased ("focal hypercellular areas").
20-25% CD34+ blasts: CD34 is a marker typically associated with hematopoietic stem cells and progenitor cells. The presence of 20-25% blasts (immature cells) suggests a possible hematologic malignancy, such as leukemia or myelodysplastic syndrome, but it would require further studies for confirmation.
In summary, the report indicates an abnormal bone marrow with an increased number of immature cells (blasts), and further testing is needed to determine the cause of these findings, including the possibility of a hematologic disorder. It’s essential to follow up with a healthcare provider or hematologist for interpretation in the context of the patient's symptoms and clinical history.
AML FISH panel: Loss at 7q22/q36.
In the context of an AML (acute myeloid leukemia) FISH (fluorescence in situ hybridization) panel, the finding of a loss at 7q22/q36 typically indicates a deletion on the long arm of chromosome 7, specifically at the regions 7q22 and 7q36.
Chromosome 7 is one of the larger chromosomes in the human genome, and it is often involved in various genetic alterations, including deletions and mutations, in several cancers.
7q22 and 7q36 refer to specific regions on the chromosome 7 long arm (denoted as "q"). Deletions in these areas can be associated with a variety of hematologic malignancies, including AML.
Loss of material at these loci might affect genes that play important roles in cell growth, survival, or differentiation, contributing to the development of leukemia.
Clinical Significance:
Deletions involving chromosome 7 or parts of it, such as at 7q22/q36, are often seen in myelodysplastic syndromes (MDS), AML, and other hematologic malignancies.
This specific deletion may be linked to poor prognosis in AML, though its impact depends on other co-occurring genetic abnormalities.
It is essential to interpret this result in the context of other genetic findings, clinical features, and the patient’s overall health status.
Your oncologist or hematologist will be able to give you further insights into the clinical significance of this finding for the individual patient.
Flow cytometry is a very poor quality sample (only 5.85% intact single cells) but there is apopulation of CD34+CD117+HLADR+CD33+CD7+CD13+CD15wk blasts and by intracellularstaining CD34+CD117+HLADR+CD33+CD7+CD13+CD15wk (approx 28% of the intactsingle cells).Negative for the FLT3-ITD.
This additional information provides further details about the flow cytometry analysis, which helps in the assessment of the bone marrow sample. Here's a breakdown:
Poor quality sample: The flow cytometry sample was of poor quality, with only 5.85% intact single cells available for analysis, which can limit the interpretability of the results. However, despite this, a population of abnormal cells was still detected.
Blasts identified: There is a population of CD34+CD117+HLADR+CD33+CD7+CD13+CD15wk blasts. These markers are commonly found on immature cells (blasts) that could be indicative of a hematologic malignancy, such as leukemia. Here’s what the markers suggest:
CD34: A stem cell marker often expressed on immature hematopoietic cells.
CD117 (c-Kit): A marker for early hematopoietic progenitor cells.
HLADR: A marker associated with the activation of hematopoietic cells.
CD33: A myeloid marker typically found on myeloid lineage blasts.
CD7: A marker of T-cells, often expressed in some hematologic malignancies, including myeloid leukemias.
CD13: Another myeloid marker often seen on myeloblasts.
CD15 (weak expression): A marker usually seen in granulocytic lineage cells; weak expression can be seen on myeloid blasts.
Approx. 28% of intact single cells: This percentage indicates that approximately 28% of the intact cells in the sample are the described population of blasts. This is a significant finding, as a high blast count can be suggestive of a myeloproliferative disorder or acute leukemia.
Negative for FLT3-ITD: The absence of the FLT3-ITD (internal tandem duplication) mutation is an important finding. FLT3-ITD is a mutation that is often associated with poor prognosis in acute myeloid leukemia (AML), particularly with higher blast counts. Its negative status can help rule out this specific mutation as a contributing factor to the malignancy, although the presence of other mutations could still be relevant.
Conclusion: The flow cytometry data suggests the presence of an abnormal population of myeloid blasts, which could point to a myeloproliferative disorder or acute leukemia, although the sample quality is suboptimal. The negative result for FLT3-ITD is helpful but does not rule out other mutations or diagnoses. Further studies, including a repeat sample with better quality or additional molecular testing, will be crucial for a more accurate diagnosis.
Targeted Therapies and FLT3 Inhibitors
Mutations in the FLT3 gene are among the most common genetic alterations in AML, often associated with poor prognosis. FLT3 inhibitors, such as gilteritinib and quizartinib, have been developed to target these mutations. Gilteritinib, a dual FLT3-AXL tyrosine kinase inhibitor, received FDA approval in November 2018 for treating relapsed or refractory AML with FLT3 mutations. Similarly, quizartinib was approved in July 2023 for newly diagnosed FLT3-ITD-positive AML, to be used in combination with standard chemotherapy and as maintenance monotherapy following consolidation chemotherapy.
Combination Therapies
Recent clinical trials have explored novel combination therapies to enhance treatment efficacy. At the American Society of Hematology meeting in December 2024, a study involving patients with relapsed or refractory advanced AML reported an 82% overall response rate using a combination of revumenib (a menin inhibitor), venetoclax, and decitabine/cedazuridine. Nearly half of the participants achieved complete remission. Another trial demonstrated a 94% overall response rate with the combination of ivosidenib, venetoclax, and azacitidine in patients with AML and related syndromes, with a three-year overall survival rate of 70.5%.
Measurable Residual Disease (MRD) and Precision Medicine
Advancements in detecting measurable residual disease (MRD) have improved the ability to monitor treatment response and predict relapse. Research led by Dr. Christopher Hourigan has shown that interventions targeting MRD can enhance survival rates. Additionally, personalized single-cell sequencing techniques have been developed to distinguish between malignant and non-malignant cells, facilitating more precise treatment strategies.
Epigenetic Therapies
Epigenetic modifications play a crucial role in AML pathogenesis. The FDA has approved epigenetic-modifying drugs like ivosidenib and enasidenib for patients ineligible for intensive chemotherapy, specifically targeting IDH1 and IDH2 mutations. Ongoing research aims to validate the efficacy of these therapies and explore their integration into standard treatment protocols.
Supportive Care and Quality of Life
Advancements in supportive care, including less toxic chemotherapy regimens and immunotherapies, have improved patients' quality of life during treatment. These developments have led to better management of treatment-related side effects and enhanced overall patient well-being.
In conclusion, ongoing research and clinical trials continue to refine and expand treatment options for AML, aiming to improve survival rates and quality of life for patients.
Promising Advances in Leukemia Treatment and Patient Care
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Hi, I hope you are doing well, and hopefully in remission. I had remission just over 2 years ago, and still in remission.
kol tuv and chag sameach
Eddie