CORRELATIONS AMONG CFU-GM GROWTH PATTERNS AND ACUTE LEUKEMIA WHO-2008 ENTITIES

Background:

Acute leukemias (AL) represent a very heterogeneous and very large group of diseases that were divided into several subgroups (categories) defined by similar characteristics of their individual entities in the World Health Organization (WHO) Classification in 2008. Different growth patterns of granulocyte-macrophage colony forming cells (CFU-GM) from diagnostic bone marrows from patients with various types of AL have been described, especially depending on the stimulating factors used and the type of AL.

Aims:

To correlate the CFU-GM growth patterns of diagnostic bone marrow (BM) cells from 103 patients with AL classified according to the WHO-AL categories, entities and prognosis.

Methods:

CFU-GM were assayed  in triplicate in 1 ml agar cultures containing  2 x 10e5 nucleated BM cells, Iscove’s modified Dulbecco’s medium, 20 % fetal calf serum, and 5 % of the human bladder carcinoma cell line 5637 conditioned medium as a source of cytokines. After 7 days of incubation the number of colonies (consisting of 40 or more cells) and clusters (3-39 cells) were counted. Informed consent was obtained from all patients.

Results:

BM from 42 healthy BM donors produced 20-150 colonies and 20-150 clusters per 10e5 seeded BM nucleated cells. Low growth of colonies and high growth of clusters (L-H growth pattern) was found in 8/10 acute myeloid leukemia (AML) M3, 3/3 AML M2 with t(8;21) and 1/1 AML M4Eo case. Low growth of colonies and low growth of clusters (L-L growth pattern) exhibited BM cells of all 4 cases with near-tetraploid AML with myelodysplasia related changes (AML/MDRC). BM from other 36 AML/MDRC cases showed 13x L-L, 9x L-H, 5x L-N (low-normal), 1x N-H, and 8x H-H growth patterns of colonies and clusters. In 22 AML without MDRC the following growth patterns of CFU-GM colonies and clusters were found: 11x L-L, 6x L-H, 3x L-N, 3x N-H. All BM from 28 patients with various types of acute lymphoid leukemia (ALL) exhibited low growth of CFU-GM colonies and clusters (L-L growth pattern).

Summary / Conclusion:

Several categories of AL seem to be associated with one type of CFU-GM growth pattern that is typical for each category. Diagnostic bone marrows from patients with AML M3 and AML M2 with t(8;21) exhibited the CFU-GM growth pattern with low growth of colonies and high growth of clusters (L-H). Diagnostic BM from patients with near-tetraploid AML/MDRC exhibited the pattern with low growth of colonies and low growth of clusters (L-L). Low growth of CFU-GM colonies and clusters was found in diagnostic bone marrows from all patients with ALL studied. A special finding was a group of 8 patients with the CFU-GM growth pattern with high colonies and high clusters (H-H) who all were from the AML/MDRC WHO category only and had a very bad prognosis even in comparison to the other nonH-H AML/MDRC. Three of these 8 patients died early within 2-11 days since diagnosis, none of the 5 remaining cases reached complete remission after 3/7 induction treatment and none was a long-term survivor.

Email address: plemez@post.cz

Keywords: Acute leukemia, Clinical outcome, Colony assay, Progenitor cell

Abstrakta v časopise Haematologica 2013, Suppl1

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