In this communication we emphasize the interconnectedness of hematologic neoplasms and their developmental processes, as well as propose new diagnostic classifications for a variety of hematologic disorders. We sought to produce a comprehensive and accurate review of hematologic disorders based on updated medical research, but also connect them as transitional forms of distinct neoplastic processes ("subvectors") that, despite the various lineage-specific phenotypes,
repeat a fundamental auto-oncogenic progression (an auto-oncogenic vector) of pre-neoplastic,
chronic, subacute and acute (or terminal) stages. Auto-oncogenic theory suggests that the main causation of acquired post-adaptive malignancies involves hypoxic or hypoxia-like factors that chronically impair respiratory metabolism and adversely affect, first and foremost, the red blood cell compartment, both in its functional role and in its formative process (erythropoiesis). In the present communication, we extend the proposed etiology to hematologic neoplasms, to include deregulated
humoral and cellular auto-immune responses to RBCs and their precursors as one of the main pathways, if not the dominant one, for the induction of myeloid and lymphoid neoplasms.
First, we review the multiplicity of disorders that result in anemia or in erythroid/myeloid
polycythemias, with an emphasis on the problems associated with determining the correct etiology of
Polycythemia vera(PV) and the so-called myelodysplastic syndrome (MDS) that includes refractory
anemias. We suggest that the chronic myeloproliferative disorders (PV; Essential Thrombocytosis, ET;
Primary Myelofibrosis, PMF; and other neoplasms, including Refractory Anemia with Ring
Sideroblastosis and Thrombocytosis, RARS-T) should be viewed as auto-oncogenic, chronic blood
neoplasms, that differ in their phenotype by altered lineage-specific cytokine responses, but are simply variants of a myeloid stem cell neoplasia that has in common the JAK2V617F adaptive mutation.
In the second part, we review the myeloid leukemias, and the lymphoid and lymphomatoid
neoplasms, but, with a few exceptions, restrict ourselves to auto-oncogenic malignancies - unlike our
approach to the anemias and the polycythemias, which included all possible etiologies, not just auto-oncogenic ones.
In the domain of the myeloid leukemias, we stress in particular:
(1) the existence of an erythroleukemic vector that encompasses chronic phases like PV or
Refractory Anemia with Ring Sideroblastosis (or, still, the early stages of typical and atypical CML,
which often present a chronic erythroleukemic picture), pre-acute crises like those observed in PMF
and MDS, and acute phases like those of acute erythroblastic leukemia and other forms of acute myelogenous leukemia; and
(2) the progression of this vector to encompass a wider myeloid leukemic vector, joining in
with the auto-oncogenic, Philadelphia chromosome-positive vector linking chronic myeloid
leukemias, acute myelogenous leukemias, B cell acute lymphoblastic leukemia and biphenotypic
In the domain of the lymphoid leukemias, we stress their connection, together with the
hemolytic anemias caused by cellular or humoral auto-reactivity, to disturbed auto-immunity whose
dominant target is the erythroid compartment. We suggest that this anti-RBC reactivity is a neoplastic response to the biological degradation of RBC function and formation. If initiation of disturbed
poietic or immunologic auto-oncogenic responses is promoted by hypoxia-induced RBC fragility and
dysfunctionality, then it becomes clear why altered erythropoiesis and RBC clearance are dominant in the
etiology of acquired blood neoplasms.