Latest Research News on Myeloid Leukemia: Jan – 2020

Chronic Myeloid Leukemia

In the past decade clinical and laboratory studies have led to big new insights into the biology of chronic chronic myelocytic leukemia (CML). Basic science has defined the molecular pathogenesis of CML as unregulated signal transduction by a tyrosine kinase. Clinical science has demonstrated that it’s curable through immune-mediated elimination of leukemia cells by allogeneic T lymphocytes.Clinical FeaturesCML may be a malignant clonal disorder of hematopoietic stem cells that leads to increases in not only myeloid cells but also erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia within the bone marrow (Figure 1A, Figure 1B, andFigure 1C). [1]

Age and acute myeloid leukemia

We conducted a retrospective analysis of 968 adults with acute chronic myelocytic leukemia (AML) on 5 recent Southwest Oncology Group trials to know how the character of AML changes with age. Older study patients with AML presented with poorer performance status, lower white blood corpuscle counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. the share of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. [2]

Acute Myeloid Leukemia

Acute chronic myelocytic leukemia (AML) is characterized by a rise within the number of myeloid cells within the marrow and an arrest in their maturation, frequently leading to hematopoietic insufficiency (granulocytopenia, thrombocytopenia, or anemia), with or without leukocytosis. within the us , the annual incidence of AML is approximately 2.4 per 100,000,1 and it increases progressively with age, to a peak of 12.6 per 100,000 adults 65 years aged or older. Until the 1970s, the diagnosis was based solely on the pathological and cytologic examination of bone marrow and blood. Five-year survival rates during this era were but 15. [3]

Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q)

Myelodysplastic syndrome with isolated del(5q) may be a well-recognized entity with a comparatively favorable prognosis. Isolated del(5q) in acute chronic myelocytic leukemia is rare and acute chronic myelocytic leukemia cases with isolated del(5q) aren’t well characterized. Del(5q) has been shown to be a poor prognostic marker in acute chronic myelocytic leukemia supported multivariable analysis in large cohort studies, which contained mostly cases with del(5q) within the context of multiple chromosomal abnormalities. To further characterize acute chronic myelocytic leukemia with isolated del(5q), clinicopathologic characterization including mutation analysis was performed. [4]

Impact of DNMT3A Gene Mutation on Response of Acute Myeloid Leukemia Patients to Induction Therapy

Aim: to guage the frequency and prognostic impact of DNA methyltransferase 3A (DNMT3A) point mutation on response to induction therapy in newly diagnosed acute chronic myelocytic leukemia patients.

Study Design: Cross-sectional descriptive study.

Place and Duration: Hematology units of Suez Canal and Ain Shams schools of drugs , Egypt. Between September 2016 and July 2017.

Methodology: The study enrolled forty patients (male: female ratio was 1; mean age was 52.4 ± 19.4 years) with newly diagnosed de novo AML before starting induction therapy. DNMT3A mutations were detected using dye terminator sequencing technique for the second a part of DNMT3A, encompassing the PHD and methyltransferase domains and representing exons 11 till the last exon 23. Hematological, cytogenetic studies and DNMT3A mutation results were compared to the patients’ hematological response to induction therapy. [5]

Reference

[1] Sawyers, C.L., 1999. Chronic myeloid leukemia. New England Journal of Medicine, 340(17), (Web Link)

[2] Appelbaum, F.R., Gundacker, H., Head, D.R., Slovak, M.L., Willman, C.L., Godwin, J.E., Anderson, J.E. and Petersdorf, S.H., 2006. Age and acute myeloid leukemia. Blood, 107(9), (Web Link)

[3] Lowenberg, B., Downing, J.R. and Burnett, A., 1999. Acute myeloid leukemia. New England Journal of Medicine, 341(14), (Web Link)

[4] Acute myeloid leukemia with isolated del(5q) is associated with IDH1/IDH2 mutations and better prognosis when compared to acute myeloid leukemia with complex karyotype including del(5q)
Bryan Rea, Nidhi Aggarwal, Svetlana A. Yatsenko, Nathanael Bailey & Yen-Chun Liu
Modern Pathology (2019) (Web Link)

[5] G. Segai, D., Ramsis, N., Fahmy, H. and Kamel, N. (2018) “Impact of DNMT3A Gene Mutation on Response of Acute Myeloid Leukemia Patients to Induction Therapy”, International Blood Research & Reviews, 8(3), (Web Link)