Table 3.

Classification of stem cells in preleukemia and leukemia patients and clinical implications

Stem cell class	Major clinical implications
Normal stem cells	Can be detected in patients with leukemia and preleukemic conditionsa Basis of curative drug therapies (regeneration of normal BM)
Pre-L-NSC	(1) Can produce a preleukemic neoplastic condition, such as MDS or MPN
	(2) Can transform into LSC and thereby trigger a full-blown leukemia, such as AML
	(3) Often escapes interventional therapy, including poly-chemotherapy and targeted therapies
	(4) Can cause a late relapse after therapyb
	(5) Can increase the risk of thromboembolic events (when ARCH mutations are expressed)
LSC	Produce an overt leukemia; are often resistant against conventional chemotherapy and can cause early relapse or drug-resistant disease
	These cells need to be eradicated to achieve a complete remission (CR) after chemotherapy. In many patients long-term CR is achievedb

BM bone marrow Pre-L-NCS pre-leukemic neoplastic stem cells, MDS myelodysplastic syndrome, MPN myeloproliferative neoplasms, AML acute myeloid leukemia, ARCH age-related clonal hematopoiesis

^aPreleukemic conditions are all clonal processes that may precede a leukemia; preleukemic neoplasms are all overt hematopoietic neoplasms that can precede a leukemia

^bWhen all Pre-L-NSC and LSC can be eradicated therapy is curative and no relapse can occur. When all LSC but only some or most Pre-L-NSC can be eradicated, the patient may or may not enter long-term CR, depending on the progression potential of the residual Pre-L-NSC