All blood cells are made in the bone marrow, arising from stem cells.  There are two types of stem cells, based on the blood cells they differentiate into:  myeloid and lymphoid. Myeloid stem cells differentiate into RBCs, monocytes or platelets. Lymphoid stem cells differentiate into specialized white blood cells known as lymphocytes:  T, B, and natural killer (NK) cells.

While in bone marrow, stem cells respond to various chemical factors which determine which mature blood cell it is to become.  For example the hormone erythropoietin will act on a myeloid stem cell to develop first into a blast and, with further exposure to erythropoietin, will develop into the mature red blood cell. Further chemical stimulation will then force those blasts to differentiate into the mature form of blood cell.

Leukemia is a cancer of blood stem cells and are named based on the affected stem cell:  myeloid or lymphoid leukemia. Leukemia involves a genetic mutation that promotes overproduction of blasts such that they don’t fully differentiate into mature blood cells. Over time, they will out-number the normal stem cells and replace mature blood cells within the bone marrow.  As such, the bone marrow becomes overcrowded with abnormal blasts and the end result is a reduced number of normal mature blood cells in the peripheral blood. It’s this replacement and low counts of mature cells that often causes the patient’s clinical manifestations.

Lymphocytic leukemia (a.k.a. lymphoblastic leukemia) is caused by abnormal lymphoid stem cells leading to abnormally made T or B cells. Conversely, myelogenous leukemias are a result of abnormal myeloid stem cells, resulting in abnormal RBCs, granulocytes (e.g. neutrophils, monocytes), and/or platelets.

Leukemia can then be further subdivided into how quickly the cancer develops.  Signs and symptoms of acute leukemias start suddenly – within days or weeks. Chronic leukemias slow manifest, sometimes insidiously, over months or even years.

Acute Lymphoblastic Leukemia (ALL)

For reasons not yet determined, Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood.^[1]  ALL involves an excess production of immature blasts that matches most closely to lymphocytes (i.e. lymphoblasts).  The production of these leukemic lymphoblasts is so excessive that it physically takes up all of the room within the bone marrow, and the nutrients needed, causing a decreased hematopoiesis .  As a result, bone marrow is replaced with these leukemic lymphoblasts and eventually spill out into the peripheral blood.

Normally, ALL patients present with symptoms associated with the loss of normal formed elements (ie erythrocytes, leukocytes, or platelets), and not due to the excessive lymphoblasts. For example, an ALL patient may present to a health care provider for severe anemia.  The anemia is due to loss of erythrocytes since ALL has taken over the bone marrow such that proper erythropoiesis isn’t possible. An ALL patient with low blood cells counts is described as being pancytopenic (pan-= all, cyto = cells, penia = lack of within the blood).  Pancytopenic patients are very vulnerable to low oxygen carrying (no RBCs), infections (no WBCs), and bleeding (no platelets) and can thus, present with any one or all of these.

Watch this videolesson of author Theodore Lam looking at peripheral blood smears of an acute lymphobastic leukemia and chronic myelogenous leukemia

^{Created and recorded by Shing Tat Theodore Lam. Licensed under All Rights Reserved}

^{Created and  narrated by Shing Tat Theodore Lam. Visuals created by Sarah Pinault. Licensed under All Rights Reserved}

Section Review

Leukemia is a cancer involving an overproduction of abnormal blood cells called blasts in the bone marrow.  These immature blasts don’t function properly and replace normal hemopoiesis within the bone marrow.  Leukemia involve a mutation of a hemaopoietic stem cell either from the myeloid or lymphoid lines, thus creating multiple copies of leukemic blasts.  The most common manifestation of leukemia is the lack of one or more mature blood cells (formed elements) in the peripheral circuation, resulting in problems with bleeding, anemia, and/or infection. Leukemia can be further classified by how quickly it develops:  acute vs chronic.

Review Questions